Effects of anabolic-androgens on brain reward function

Frontiers in Neuroscience

Volumn 9, Issue AUG, 2015, Pages

  Mhillaj, Emanuela ^a   Morgese, Maria G ^b   Tucci, Paolo ^b   Bove, Maria ^a   Schiavone, Stefania ^b   Trabace, Luigia ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF FOGGIA   (Italy)

Author keywords

Anabolic androgenic steroid; Depression; Dopamine; Psychosis spectrum disorders; Reward; Serotonin

Indexed keywords

ANDROGEN; ANDROGEN ANABOLIC STEROID; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; DOPAMINE 4 RECEPTOR; DOPAMINE TRANSPORTER; MESSENGER RNA; SEROTONIN RECEPTOR; TESTOSTERONE; UNCLASSIFIED DRUG;

AGGRESSION; ANDROGEN DEFICIENCY; ANGIONEUROTIC EDEMA; BEHAVIOR CHANGE; BRAIN FUNCTION; CACHEXIA; CHRONIC DRUG ADMINISTRATION; DEPRESSION; DOPAMINE RELEASE; DOPAMINERGIC SYSTEM; DOWN REGULATION; DRUG ABUSE; DRUG DEPENDENCE; DRUG EFFICACY; DRUG SAFETY; FEMALE INFERTILITY; GENE EXPRESSION; HEART ARRHYTHMIA; HEART DISEASE; HEART FAILURE; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HEMATOLOGIC DISEASE; HEPATITIS; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; INSULIN RESISTANCE; INTRACELLULAR SIGNALING; KIDNEY FAILURE; LIVER INJURY; MENSTRUAL IRREGULARITY; METABOLIC DISORDER; MOOD DISORDER; MYOCYTOLYSIS; NONHUMAN; NYMPHOMANIA; OUTCOME ASSESSMENT; PNEUMONIA; PRESCRIPTION; PROTEIN EXPRESSION; RECEPTOR BINDING; REINFORCEMENT; REVIEW; REWARD; SEROTONINERGIC SYSTEM; SUICIDE; TESTIS ATROPHY; TESTOSTERONE BLOOD LEVEL; UPREGULATION; WITHDRAWAL SYNDROME;

EID: 84940746239     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2015.00295     Document Type: Review

References (165)

1. Aitken, C., Delalande, C., and Stanton, K. (2002). Pumping iron, risking infection? Exposure to hepatitis C, hepatitis B and HIV among anabolic-androgenic steroid injectors in Victoria, Australia. Drug Alcohol Depend. 65, 303-308. doi: 10.1016/S0376-8716(01)00174-0.
2. Alexander, G.M., Packard, M.G., and Hines, M. (1994). Testosterone has rewarding affective properties in male rats: implications for the biological basis of sexual motivation. Behav. Neurosci. 108, 424-428. doi: 10.1037/0735-7044.108.2.424.
3. Ambar, G., and Chiavegatto, S. (2009). Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice. Genes Brain Behav. 8, 161-173. doi: 10.1111/j.1601-183X.2008.00458.x.
4. Anderson, R.A., and Wu, F.C. (1996). Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate. J. Clin. Endocrinol. Metab. 81, 896-901.
5. Arnedo, M.T., Salvador, A., Martinez-Sanchis, S., and Gonzalez-Bono, E. (2000). Rewarding properties of testosterone in intact male mice: a pilot study. Pharmacol. Biochem. Behav. 65, 327-332. doi: 10.1016/S0091-3057(99)00189-6.
6. Arnedo, M.T., Salvador, A., Martínez-Sanchís, S., and Pellicer, O. (2002). Similar rewarding effects of testosterone in mice rated as short and long attack latency individuals. Addict. Biol. 7, 373-379. doi: 10.1080/1355621021000005955.
7. Arvary, D., and Pope, H.G. Jr. (2000). Anabolic-androgenic steroids as a gateway to opioid dependence. N. Engl. J. Med. 342, 1532. doi: 10.1056/NEJM200005183422018.
8. Baggish, A.L., Weiner, R.B., Kanayama, G., Hudson, J.I., Picard, M.H., Hutter, A.M. Jr., et al. (2010). Long-term anabolic-androgenic steroid use is associated with left ventricular dysfunction. Circ. Heart Fail. 3, 472-476. doi: 10.1161/CIRCHEARTFAILURE.109.931063.
9. Bahrke, M.S., and Yesalis, C.E. III. (1994). Weight training. A potential confounding factor in examining the psychological and behavioural effects of anabolic-androgenic steroids. Sports Med. 18, 309-318. doi: 10.2165/00007256-199418050-00003.
10. Ballard, C.L., and Wood, R.I. (2005). Intracerebroventricular self-administration of commonly abused anabolic-androgenic steroids in male hamsters (Mesocricetus auratus): nandrolone, drostanolone, oxymetholone, and stanozolol. Behav. Neurosci. 119, 752-758. doi: 10.1037/0735-7044.119.3.752.
11. Basaria, S., Wahlstrom, J.T., and Dobs, A.S. (2001). Clinical review 138: anabolic-androgenic steroid therapy in the treatment of chronic diseases. J. Clin. Endocrinol. Metab. 86, 5108-5117. doi: 10.1210/jcem.86.11.7983.
12. Bhasin, S., Storer, T.W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., et al. (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N. Engl. J. Med. 335, 1-7. doi: 10.1056/NEJM199607043350101.
13. Bhasin, S., Woodhouse, L., Casaburi, R., Singh, A.B., Bhasin, D., Berman, N., et al. (2001). Testosterone dose-response relationships in healthy young men. Am. J. Physiol. Endocrinol. Metab. 281, E1172-E1181.
14. Birgner, C., Kindlundh-Hogberg, A.M., Alsio, J., Lindblom, J., Schioth, H.B., and Bergstrom, L. (2008a). The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors. Brain Res. 1240, 221-228. doi: 10.1016/j.brainres.2008.09.003.
15. Birgner, C., Kindlundh-Högberg, A.M., Nyberg, F., and Bergström, L. (2007). Altered extracellular levels of DOPAC and HVA in the rat nucleus accumbens shell in response to sub-chronic nandrolone administration and a subsequent amphetamine challenge. Neurosci. Lett. 412, 168-172. doi: 10.1016/j.neulet.2006.11.001.
16. Birgner, C., Kindlundh-Högberg, A.M., Oreland, L., Alsiö, J., Lindblom, J., Schiöth, H.B., et al. (2008b). Reduced activity of monoamine oxidase in the rat brain following repeated nandrolone decanoate administration. Brain Res. 1219, 103-110. doi: 10.1016/j.brainres.2008.05.014.
17. Bonson, K.R., Johnson, R.G., Fiorella, D., Rabin, R.A., and Winter, J.C. (1994). Serotonergic control of androgen-induced dominance. Pharmacol. Biochem. Behav. 49, 313-322. doi: 10.1016/0091-3057(94)90427-8.
18. Breuer, M.E., McGinnis, M.Y., Lumia, A.R., and Possidente, B.P. (2001). Aggression in male rats receiving anabolic androgenic steroids: effects of social and environmental provocation. Horm. Behav. 40, 409-418. doi: 10.1006/hbeh.2001.1706.
19. Brower, K.J. (1997). Withdrawal from anabolic steroids. Curr. Ther. Endocrinol. Metab. 6, 338-343.
20. Brower, K.J. (2000). "Anabolic steroids: potential for physical and psychological dependence," in Anabolic Steroids in Sport and Exercise, 2nd Edn., ed C. E. Yesalis (Champaign, IL: Human Kinetics), 280-304.
21. Brower, K.J. (2002). Anabolic steroid abuse and dependence. Curr. Psychiatry Rep. 4, 377-387. doi: 10.1007/s11920-002-0086-6.
22. Brower, K.J., Blow, F.C., Young, J.P., and Hill, E.M. (1991). Symptoms and correlates of anabolic-androgenic steroid dependence. Br. J. Addict. 86, 759-768. doi: 10.1111/j.1360-0443.1991.tb03101.x.
23. Brower, K.J., Eliopulos, G.A., Blow, F.C., Catlin, D.H., and Beresford, T.P. (1990). Evidence for physical and psychological dependence on anabolic androgenic steroids in eight weight lifters. Am. J. Psychiatry 147, 510-512. doi: 10.1176/ajp.147.4.510.
24. Célérier, E., Ahdepil, T., Wikander, H., Berrendero, F., Nyberg, F., and Maldonado, R. (2006). Influence of the anabolic-androgenic steroid nandrolone on cannabinoid dependence. Neuropharmacology 50, 788-806. doi: 10.1016/j.neuropharm.2005.11.017.
25. Célérier, E., Yazdi, M.T., Castañé, A., Ghozland, S., Nyberg, F., and Maldonado, R. (2003). Effects of nandrolone on acute morphine responses, tolerance and dependence in mice. Eur. J. Pharmacol. 465, 69-81. doi: 10.1016/S0014-2999(03)01462-6.
26. Christie, M.H., and Barfield, R.J. (1979). Effects of aromatizable androgens on aggressive behaviour among rats (rattus norvegicus). J. Endocrinol. 83, 17-26. doi: 10.1677/joe.0.0830017.
27. Clark, A.S., and Barber, D.M. (1994). Anabolic-androgenic steroids and aggression in castrated male rats. Physiol. Behav. 56, 1107-1113. doi: 10.1016/0031-9384(94)90351-4.
28. Clark, A.S., and Henderson, L.P. (2003). Behavioral and physiological responses to anabolic-androgenic steroids. Neurosci. Biobehav. Rev. 27, 413-436. doi: 10.1016/S0149-7634(03)00064-2.
29. Clark, A.S., Lindenfeld, R.C., and Gibbons, C.H. (1996). Anabolic-androgenic steroids and brain reward. Pharmacol. Biochem. Behav. 53, 741-745. doi: 10.1016/0091-3057(95)02082-9.
30. Conway, A.J., Handelsman, D.J., Lording, D.W., Stuckey, B., and Zajac, J.D. (2000). Use, misuse and abuse of androgens. The Endocrine Society of Australia consensus guidelines for androgen prescribing. Med. J. Aust. 172, 220-224.
31. Cooper, S.E., and Wood, R.I. (2014). Androgens and opiates: testosterone interaction with morphine self-administration in male rats. Neuroreport 25, 521-526. doi: 10.1097/wnr.0000000000000125.
32. Coviello, A.D., Kaplan, B., Lakshman, K.M., Chen, T., Singh, A.B., and Bhasin, S. (2008). Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J. Clin. Endocrinol. Metab. 93, 914-919. doi: 10.1210/jc.2007-1692.
33. Cunningham, R.L., and McGinnis, M.Y. (2006). Physical provocation of pubertal anabolic androgenic steroid exposed male rats elicits aggression towards females. Horm. Behav. 50, 410-416. doi: 10.1016/j.yhbeh.2006.05.002.
34. Cunningham, R.L., and McGinnis, M.Y. (2007). Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty. Horm. Behav. 51, 135-141. doi: 10.1016/j.yhbeh.2006.09.003.
35. Daly, R.C., Su, T.P., Schmidt, P.J., Pickar, D., Murphy, D.L., and Rubinow, D.R. (2001). Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings. Arch. Gen. Psychiatry 58, 172-177. doi: 10.1001/archpsyc.58.2.172.
36. Dean, C.E. (2000). Prasterone (DHEA) and mania. Ann. Pharmacother. 34, 1419-1422. doi: 10.1345/aph.10115.
37. de Beun, R., Jansen, E., Slangen, J.L., and Van de Poll, N.E. (1992). Testosterone as appetitive and discriminative stimulus in rats: sex- and dose-dependent effects. Physiol. Behav. 52, 629-634. doi: 10.1016/0031-9384(92)90389-J.
38. de Souza Silva, M.A., Mattern, C., Topic, B., Buddenberg, T.E., and Huston, J.P. (2009). Dopaminergic and serotonergic activity in neostriatum and nucleus accumbens enhanced by intranasal administration of testosterone. Eur. Neuropsychopharmacol. 19, 53-63. doi: 10.1016/j.euroneuro.2008.08.003.
39. DiMeo, A.N., and Wood, R.I. (2004). Circulating androgens enhance sensitivity to testosterone self-administration in male hamsters. Pharmacol. Biochem. Behav. 79, 383-389. doi: 10.1016/j.pbb.2004.08.015.
40. Dohle, G.R., Smit, M., and Weber, R.F. (2003). Androgens and male fertility. World J. Urol. 21, 341-345. doi: 10.1007/s00345-003-0365-9.
41. DuRant, R.H., Escobedo, L.G., and Heath, G.W. (1995). Anabolic-steroid use, strength training, and multiple drug use among adolescents in the United States. Pediatrics 96, 23-28.
42. Ernst, M., Romeo, R.D., and Andersen, S.L. (2009). Neurobiology of the development of motivated behaviors in adolescence: a window into a neural systems model. Pharmacol. Biochem. Behav. 93, 199-211. doi: 10.1016/j.pbb.2008.12.013.
43. Far, H.R., Ågren, G., and Thiblin, I. (2012). Cardiac hypertrophy in deceased users of anabolic androgenic steroids: an investigation of autopsy findings. Cardiovasc. Pathol. 21, 312-316. doi: 10.1016/j.carpath.2011.10.002.
44. Farrell, S.F., and McGinnis, M.Y. (2003). Effects of pubertal anabolic-androgenic steroid (AAS) administration on reproductive and aggressive behaviors in male rats. Behav. Neurosci. 117, 904-911. doi: 10.1037/0735-7044.117.5.904.
45. Ferreira, I., Brooks, D., Lacasse, Y., and Goldstein, R. (2001). Nutritional intervention in COPD: a systematic overview. Chest 119, 353-363. doi: 10.1378/chest.119.2.353.
46. Foradori, C.D., Weiser, M.J., and Handa, R.J. (2008). Non-genomic actions of androgens. Front. Neuroendocrinol. 29, 169-181. doi: 10.1016/j.yfrne.2007.10.005.
47. Franke, W.W., and Berendonk, B. (1997). Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clin. Chem. 43, 1262-1279.
48. Frye, C.A. (2007). Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol. Pharmacol. Biochem. Behav. 86, 354-367. doi: 10.1016/j.pbb.2006.10.003.
49. Frye, C.A., Babson, A., and Walf, A.A. (2007). Self-administration of 3alpha-androstanediol increases locomotion and analgesia and decreases aggressive behavior of male hamsters. Pharmacol. Biochem. Behav. 86, 415-421. doi: 10.1016/j.pbb.2006.05.025.
50. Frye, C.A., Park, D., Tanaka, M., Rosellini, R., and Svare, B. (2001). The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Psychoneuroendocrinology 26, 731-750. doi: 10.1016/S0306-4530(01)00027-0.
51. Frye, C.A., Rhodes, M.E., Rosellini, R., and Svare, B. (2002). The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5alpha-reduced metabolites. Pharmacol. Biochem. Behav. 74, 119-127. doi: 10.1016/S0091-3057(02)00968-1.
52. Furlanello, F., Bentivegna, S., Cappato, R., and De Ambroggi, L. (2003). Arrhythmogenic effects of illicit drugs in athletes. Ital. Heart J. 4, 829-837.
53. Galvan, A. (2010). Adolescent development of the reward system. Front. Hum. Neurosci. 4:6. doi: 10.3389/neuro.09.006.2010
54. Gianoulakis, C. (2009). Endogenous opioids and addiction to alcohol and other drugs of abuse. Curr. Top. Med. Chem. 9, 999-1015. doi: 10.2174/156802609789630956.
55. Grimes, J.M., and Melloni, R.H. Jr. (2005). Serotonin-1B receptor activity and expression modulate the aggression-stimulating effects of adolescent anabolic steroid exposure in hamsters. Behav. Neurosci. 119, 1184-1194. doi: 10.1037/0735-7044.119.5.1184.
56. Gupta, V., Bhasin, S., Guo, W., Singh, R., Miki, R., Chauhan, P., et al. (2008). Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol. Cell. Endocrinol. 296, 32-40. doi: 10.1016/j.mce.2008.08.019.
57. Hallberg, M., Johansson, P., Kindlundh, A.M., and Nyberg, F. (2000). Anabolic-androgenic steroids affect the content of substance P and substance P(1-7) in the rat brain. Peptides 21, 845-852. doi: 10.1016/S0196-9781(00)00218-7.
58. Harlan, R.E., Brown, H.E., Lynch, C.S., D'Souza, D., and Garcia, M.M. (2000). Androgenic-anabolic steroids blunt morphine-induced c-fos expression in the rat striatum: possible role of beta-endorphin. Brain Res. 853, 99-104. doi: 10.1016/S0006-8993(99)02257-X.
59. Harrison, R.J., Connor, D.F., Nowak, C., Nash, K., and Melloni, R.H. Jr. (2000). Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters. Psychoneuroendocrinology 25, 317-338. doi: 10.1016/S0306-4530(99)00057-8.
60. Hart, D.W., Wolf, S.E., Ramzy, P.I., Chinkes, D.L., Beauford, R.B., Ferrando, A.A., et al. (2001). Anabolic effects of oxandrolone after severe burn. Ann. Surg. 233, 556-564. doi: 10.1097/00000658-200104000-00012.
61. Hassan, N.A., Salem, M.F., and Sayed, M.A. (2009). Doping and effects of anabolic androgenic steroids on the heart: histological, ultrastructural, and echocardiographic assessment in strength athletes. Hum. Exp. Toxicol. 28, 273-283. doi: 10.1177/0960327109104821.
62. Haupt, H.A. (2001). Upper extremity injuries associated with strength training. Clin. Sports Med. 20, 481-490. doi: 10.1016/S0278-5919(05)70264-7.
63. Irving, L.M., Wall, M., Neumark-Sztainer, D., and Story, M. (2002). Steroid use among adolescents: findings from Project EAT. J. Adolesc. Health 30, 243-252. doi: 10.1016/S1054-139X(01)00414-1.
64. Johansson, P., Hallberg, M., Kindlundh, A., and Nyberg, F. (2000a). The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate. Brain Res. Bull. 51, 413-418. doi: 10.1016/S0361-9230(99)00263-4.
65. Johansson, P., Lindqvist, A., Nyberg, F., and Fahlke, C. (2000b). Anabolic androgenic steroids affects alcohol intake, defensive behaviors and brain opioid peptides in the rat. Pharmacol. Biochem. Behav. 67, 271-279. doi: 10.1016/S0091-3057(00)00365-8.
66. Johansson, P., Ray, A., Zhou, Q., Huang, W., Karlsson, K., and Nyberg, F. (1997). Anabolic androgenic steroids increase beta-endorphin levels in the ventral tegmental area in the male rat brain. Neurosci. Res. 27, 185-189. doi: 10.1016/S0168-0102(96)01141-8.
67. Johnson, L.R., and Wood, R.I. (2001). Oral testosterone self-administration in male hamsters. Neuroendocrinology 73, 285-292. doi: 10.1159/000054645.
68. Kailanto, S., Kankaanpää, A., and Seppälä, T. (2011). Subchronic steroid administration induces long lasting changes in neurochemical and behavioral response to cocaine in rats. Steroids 76, 1310-1316. doi: 10.1016/j.steroids.2011.06.011.
69. Kanayama, G., Cohane, G.H., Weiss, R.D., and Pope, H.G. (2003a). Past anabolic-androgenic steroid use among men admitted for substance abuse treatment: an underrecognized problem? J. Clin. Psychiatry 64, 156-160. doi: 10.4088/JCP.v64n0208.
70. Kanayama, G., Hudson, J.I., and Pope, H.G. Jr. (2009). Features of men with anabolic-androgenic steroid dependence: a comparison with nondependent AAS users and with AAS nonusers. Drug Alcohol Depend. 102, 130-137. doi: 10.1016/j.drugalcdep.2009.02.008.
71. Kanayama, G., Pope, H.G., Cohane, G., and Hudson, J.I. (2003b). Risk factors for anabolic-androgenic steroid use among weightlifters: a case-control study. Drug Alcohol Depend. 71, 77-86. doi: 10.1016/S0376-8716(03)00069-3.
72. Kashkin, K.B., and Kleber, H.D. (1989). Hooked on hormones? An anabolic steroid addiction hypothesis. JAMA 262, 3166-3170. doi: 10.1001/jama.1989.03430220089036.
73. Kindlundh, A.M., Bergström, M., Monazzam, A., Hallberg, M., Blomqvist, G., Långström, B., et al. (2002). Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography. Prog. Neuropsychopharmacol. Biol. Psychiatry 26, 1303-1308. doi: 10.1016/S0278-5846(02)00293-2.
74. Kindlundh, A.M., Hagekull, B., Isacson, D.G., and Nyberg, F. (2001a). Adolescent use of anabolic-androgenic steroids and relations to self-reports of social, personality and health aspects. Eur. J. Public Health 11, 322-328. doi: 10.1093/eurpub/11.3.322.
75. Kindlundh, A.M., Isacson, D.G., Berglund, L., and Nyberg, F. (1999). Factors associated with adolescent use of doping agents: anabolic-androgenic steroids. Addiction 94, 543-553. doi: 10.1046/j.1360-0443.1999.9445439.x.
76. Kindlundh, A.M., Lindblom, J., Bergström, L., Wikberg, J.E., and Nyberg, F. (2001b). The anabolic-androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain. Eur. J. Neurosci. 13, 291-296. doi: 10.1046/j.0953-816X.2000.01402.x.
77. Kindlundh, A.M., Lindblom, J., and Nyberg, F. (2003). Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D(1)- and D(2)-receptors in the rat brain. Brain Res. 979, 37-42. doi: 10.1016/S0006-8993(03)02843-9.
78. Koob, G.F. (2006). The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction 101(Suppl. 1), 23-30. doi: 10.1111/j.1360-0443.2006.01586.x.
79. Krieg, A., Scharhag, J., Albers, T., Kindermann, W., and Urhausen, A. (2007). Cardiac tissue Doppler in steroid users. Int. J. Sports Med. 28, 638-643. doi: 10.1055/s-2007-964848.
80. Kritzer, M.F., and Creutz, L.M. (2008). Region and sex differences in constituent dopamine neurons and immunoreactivity for intracellular estrogen and androgen receptors in mesocortical projections in rats. J. Neurosci. 28, 9525-9535. doi: 10.1523/JNEUROSCI. 2637-08.2008.
81. Kuhn, C.M. (2002). Anabolic steroids. Recent Prog. Horm. Res. 57, 411-434. doi: 10.1210/rp.57.1.411.
82. Kurling, S., Kankaanpää, A., and Seppälä, T. (2008). Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats. Behav. Brain Res. 189, 191-201. doi: 10.1016/j.bbr.2007.12.021.
83. Kurling-Kailanto, S., Kankaanpää, A., and Seppälä, T. (2010). Subchronic nandrolone administration reduces cocaine-induced dopamine and 5-hydroxytryptamine outflow in the rat nucleus accumbens. Psychopharmacology (Berl.) 209, 271-281. doi: 10.1007/s00213-010-1796-9.
84. Kutscher, E.C., Lund, B.C., and Perry, P.J. (2002). Anabolic steroids: a review for the clinician. Sports Med. 32, 285-296. doi: 10.2165/00007256-200232050-00001.
85. Langer, C.J., Hoffman, J.P., and Ottery, F.D. (2001). Clinical significance of weight loss in cancer patients: rationale for the use of anabolic agents in the treatment of cancer-related cachexia. Nutrition 17, S1-S20. doi: 10.1016/s0899-9007(01)80001-0.
86. Le Grevès, P., Huang, W., Johansson, P., Thörnwall, M., Zhou, Q., and Nyberg, F. (1997). Effects of an anabolic-androgenic steroid on the regulation of the NMDA receptor NR1, NR2A and NR2B subunit mRNAs in brain regions of the male rat. Neurosci. Lett. 226, 61-64. doi: 10.1016/S0304-3940(97)00244-9.
87. Li, S., Kang, L., Zhang, Y., Feng, B., Du, J., and Cui, H. (2015). Detecting the presence of hippocampus membrane androgen receptors in male SAMP8 mice and their induced synaptic plasticity. Mol. Cell. Endocrinol. 414, 82-90. doi: 10.1016/j.mce.2015.07.005.
88. Lindqvist, A.S., Johansson-Steensland, P., Nyberg, F., and Fahlke, C. (2002). Anabolic androgenic steroid affects competitive behaviour, behavioural response to ethanol and brain serotonin levels. Behav. Brain Res. 133, 21-29. doi: 10.1016/S0166-4328(01)00408-9.
89. Long, S.F., Wilson, M.C., and Davis, W.M. (2000). The effects of nandrolone decanoate on cocaine-induced kindling in male rats. Neuropharmacology 39, 2442-2447. doi: 10.1016/S0028-3908(00)00061-7.
90. Long, S.F., Wilson, M.C., Sufka, K.J., and Davis, W.M. (1996). The effects of cocaine and nandrolone co-administration on aggression in male rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 20, 839-856. doi: 10.1016/0278-5846(96)00063-2.
91. Luijkx, T., Velthuis, B.K., Backx, F.J., Buckens, C.F., Prakken, N.H., Rienks, R., et al. (2013). Anabolic androgenic steroid use is associated with ventricular dysfunction on cardiac MRI in strength trained athletes. Int. J. Cardiol. 167, 664-668. doi: 10.1016/j.ijcard.2012.03.072.
92. Lumia, A.R., and McGinnis, M.Y. (2010). Impact of anabolic androgenic steroids on adolescent males. Physiol. Behav. 100, 199-204. doi: 10.1016/j.physbeh.2010.01.007.
93. Lumia, A.R., Thorner, K.M., and McGinnis, M.Y. (1994). Effects of chronically high doses of the anabolic androgenic steroid, testosterone, on intermale aggression and sexual behavior in male rats. Physiol. Behav. 55, 331-335. doi: 10.1016/0031-9384(94)90142-2.
94. Magnusson, K., Birgner, C., Bergström, L., Nyberg, F., and Hallberg, M. (2009). Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography. Neuropeptides 43, 105-111. doi: 10.1016/j.npep.2008.12.005.
95. Magnusson, K., Hallberg, M., Bergquist, J., and Nyberg, F. (2007). Enzymatic conversion of dynorphin A in the rat brain is affected by administration of nandrolone decanoate. Peptides 28, 851-858. doi: 10.1016/j.peptides.2006.12.011.
96. Manoharan, G., Campbell, N.P., and O'Brien, C.J. (2002). Syncopal episodes in a young amateur body builder. Br. J. Sports Med. 36, 67-68. doi: 10.1136/bjsm.36.1.67.
97. Martinez-Rivera, F.J., Natal-Albelo, E.J., Martínez, N.A., Orozco-Vega, R.A., Muñiz-Seda, O.A., and Barreto-Estrada, J.L. (2015). The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice. Behav. Processes 113, 81-85. doi: 10.1016/j.beproc.2015.01.008.
98. Martínez-Sanchis, S., Brain, P.F., Salvador, A., and Simón, V.M. (1996). Long-term chronic treatment with stanozolol lacks significant effects on aggression and activity in young and adult male laboratory mice. Gen. Pharmacol. 27, 293-298. doi: 10.1016/0306-3623(95)02019-5.
99. McBride, A.J., Williamson, K., and Petersen, T. (1996). Three cases of nalbuphine hydrochloride dependence associated with anabolic steroid use. Br. J. Sports Med. 30, 69-70. doi: 10.1136/bjsm.30.1.69.
100. McGinnis, M.Y. (2004). Anabolic androgenic steroids and aggression: studies using animal models. Ann. N.Y. Acad. Sci. 1036, 399-415. doi: 10.1196/annals.1330.024.
101. McGinnis, M.Y., Lumia, A.R., Breuer, M.E., and Possidente, B. (2002a). Physical provocation potentiates aggression in male rats receiving anabolic androgenic steroids. Horm. Behav. 41, 101-110. doi: 10.1006/hbeh.2001.1742.
102. McGinnis, M.Y., Lumia, A.R., and Possidente, B.P. (2002b). Effects of withdrawal from anabolic androgenic steroids on aggression in adult male rats. Physiol. Behav. 75, 541-549. doi: 10.1016/S0031-9384(02)00657-1.
103. McQueen, J.K., Wilson, H., Sumner, B.E., and Fink, G. (1999). Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids. Brain Res. Mol. Brain Res. 63, 241-247. doi: 10.1016/S0169-328X(98)00281-2.
104. Menard, C.S., Hebert, T.J., Dohanich, G.P., and Harlan, R.E. (1995). Androgenic-anabolic steroids modify beta-endorphin immunoreactivity in the rat brain. Brain Res. 669, 255-262. doi: 10.1016/0006-8993(94)01266-K.
105. Midgley, S.J., Heather, N., and Davies, J.B. (1999). Dependence-producing potential of anabolic-androgenic steroids. Addict. Res. Theory 7, 539-550. doi: 10.3109/16066359909004404
106. Missale, C., Nash, S.R., Robinson, S.W., Jaber, M., and Caron, M.G. (1998). Dopamine receptors: from structure to function. Physiol. Rev. 78, 189-225.
107. Montisci, M., El Mazloum, R., Cecchetto, G., Terranova, C., Ferrara, S.D., Thiene, G., et al. (2012). Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases. Forensic Sci. Int. 217, e13-e18. doi: 10.1016/j.forsciint.2011.10.032.
108. Morley, J.E. (2001). Testosterone replacement in older men and women. J. Gend. Specif. Med. 4, 49-53.
109. Morton, R., Gleason, O., and Yates, W. (2000). Psychiatric effects of anabolic steroids after burn injuries. Psychosomatics 41, 66-68. doi: 10.1016/S0033-3182(00)71176-5
110. Negus, S.S., Pope, H.G. Jr., Kanayama, G., Wines, J.D. Jr., and Fischer, B.D. (2001). Lack of evidence for opioid tolerance or dependence in rhesus monkeys following high-dose anabolic-androgenic steroid administration. Psychoneuroendocrinology 26, 789-796. doi: 10.1016/S0306-4530(01)00028-2.
111. Noakes, T.D. (2004). Tainted glory-doping and athletic performance. N. Engl. J. Med. 351, 847-849. doi: 10.1056/NEJMp048208.
112. Oberlander, J.G., and Henderson, L.P. (2012). Corticotropin-releasing factor modulation of forebrain GABAergic transmission has a pivotal role in the expression of anabolic steroid-induced anxiety in the female mouse. Neuropsychopharmacology 37, 1483-1499. doi: 10.1038/npp.2011.334.
113. Packard, M.G., Cornell, A.H., and Alexander, G.M. (1997). Rewarding affective properties of intra-nucleus accumbens injections of testosterone. Behav. Neurosci. 111, 219-224. doi: 10.1037/0735-7044.111.1.219.
114. Parkinson, A.B., and Evans, N.A. (2006). Anabolic androgenic steroids: a survey of 500 users. Med. Sci. Sports Exerc. 38, 644-651. doi: 10.1249/01.mss.0000210194.56834.5d.
115. Parrilla-Carrero, J., Figueroa, O., Lugo, A., Garcia-Sosa, R., Brito-Vargas, P., Cruz, B., et al. (2009). The anabolic steroids testosterone propionate and nandrolone, but not 17alpha-methyltestosterone, induce conditioned place preference in adult mice. Drug Alcohol Depend. 100, 122-127. doi: 10.1016/j.drugalcdep.2008.09.014.
116. Pärssinen, M., and Seppälä, T. (2002). Steroid use and long-term health risks in former athletes. Sports Med. 32, 83-94. doi: 10.2165/00007256-200232020-00001.
117. Peters, K.D., and Wood, R.I. (2005). Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms. Neuroscience 130, 971-981. doi: 10.1016/j.neuroscience.2004.09.063.
118. Philipova, T., Ivanova, T., Pavlova, E., Kasakov, L., and Vlaskovska, M. (2003). Nandrolone modulates the non-opioid and opioid analgesia and tolerance/dependence: role of sexual dimorphism. Arch. Physiol. Biochem. 111, 429-436. doi: 10.3109/13813450312331342283.
119. Polsky, B., Kotler, D., and Steinhart, C. (2001). HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment. AIDS Patient Care STDS 15, 411-423. doi: 10.1089/108729101316914412.
120. Pope, H.G. J., and Brower, K.J. (2000). "Anabolic-androgenic steroid abuse," in Comprehensive Textbook of Psychiatry, eds B. J. Sadock, V.A. Sadock, and P. Ruiz, (Philadelphia, PA: Lippincott Williams & Wilkins), 1085-1095.
121. Pope, H.G. Jr., Kouri, E.M., and Hudson, J.I. (2000). Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Arch. Gen. Psychiatry 57, 133-140. discussion 155-136. doi: 10.1001/archpsyc.57.2.133.
122. Pope, H.G. Jr., Wood, R.I., Rogol, A., Nyberg, F., Bowers, L., and Bhasin, S. (2014). Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr. Rev. 35, 341-375. doi: 10.1210/er.2013-1058.
123. Porcerelli, J.H., and Sandler, B.A. (1995). Narcissism and empathy in steroid users. Am. J. Psychiatry 152, 1672-1674. doi: 10.1176/ajp.152.11.1672.
124. Rabkin, J.G., Wagner, G.J., and Rabkin, R. (2000). A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch. Gen. Psychiatry 57, 141-147. discussion 155-146. doi: 10.1001/archpsyc.57.2.141.
125. Ricci, L.A., Grimes, J.M., and Melloni, R.H. Jr. (2007). Lasting changes in neuronal activation patterns in select forebrain regions of aggressive, adolescent anabolic/androgenic steroid-treated hamsters. Behav. Brain Res. 176, 344-352. doi: 10.1016/j.bbr.2006.10.025.
126. Ricci, L.A., Rasakham, K., Grimes, J.M., and Melloni, R.H. Jr. (2006). Serotonin-1A receptor activity and expression modulate adolescent anabolic/androgenic steroid-induced aggression in hamsters. Pharmacol. Biochem. Behav. 85, 1-11. doi: 10.1016/j.pbb.2006.06.022.
127. Roberto, M., Cruz, M.T., Gilpin, N.W., Sabino, V., Schweitzer, P., Bajo, M., et al. (2010). Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence. Biol. Psychiatry 67, 831-839. doi: 10.1016/j.biopsych.2009.11.007.
128. Roberto, M., Madamba, S.G., Stouffer, D.G., Parsons, L.H., and Siggins, G.R. (2004). Increased GABA release in the central amygdala of ethanol-dependent rats. J. Neurosci. 24, 10159-10166. doi: 10.1523/JNEUROSCI. 3004-04.2004.
129. Salas-Ramirez, K.Y., Montalto, P.R., and Sisk, C.L. (2010). Anabolic steroids have long-lasting effects on male social behaviors. Behav. Brain Res. 208, 328-335. doi: 10.1016/j.bbr.2009.11.026.
130. Sato, S.M., Johansen, J.A., Jordan, C.L., and Wood, R.I. (2010). Membrane androgen receptors may mediate androgen reinforcement. Psychoneuroendocrinology 35, 1063-1073. doi: 10.1016/j.psyneuen.2010.01.007.
131. Sato, S.M., Schulz, K.M., Sisk, C.L., and Wood, R.I. (2008). Adolescents and androgens, receptors and rewards. Horm. Behav. 53, 647-658. doi: 10.1016/j.yhbeh.2008.01.010.
132. Schlussman, S.D., Zhou, Y., Johansson, P., Kiuru, A., Ho, A., Nyberg, F., et al. (2000). Effects of the androgenic anabolic steroid, nandrolone decanoate, on adrenocorticotropin hormone, corticosterone and proopiomelanocortin, corticotropin releasing factor (CRF) and CRF receptor1 mRNA levels in the hypothalamus, pituitary and amygdala of the rat. Neurosci. Lett. 284, 190-194. doi: 10.1016/S0304-3940(00)01016-8.
133. Schroeder, J.P., and Packard, M.G. (2000). Role of dopamine receptor subtypes in the acquisition of a testosterone conditioned place preference in rats. Neurosci. Lett. 282, 17-20. doi: 10.1016/S0304-3940(00)00839-9.
134. Schwartzer, J.J., Ricci, L.A., and Melloni, R.H. Jr. (2009). Adolescent anabolic-androgenic steroid exposure alters lateral anterior hypothalamic serotonin-2A receptors in aggressive male hamsters. Behav. Brain Res. 199, 257-262. doi: 10.1016/j.bbr.2008.11.048.
135. Shahidi, N.T. (2001). A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin. Ther. 23, 1355-1390. doi: 10.1016/S0149-2918(01)80114-4.
136. Singh, R., Artaza, J.N., Taylor, W.E., Braga, M., Yuan, X., Gonzalez-Cadavid, N.F., et al. (2006). Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology 147, 141-154. doi: 10.1210/en.2004-1649.
137. Singh, R., Artaza, J.N., Taylor, W.E., Gonzalez-Cadavid, N.F., and Bhasin, S. (2003). Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144, 5081-5088. doi: 10.1210/en.2003-0741.
138. Sinha-Hikim, I., Artaza, J., Woodhouse, L., Gonzalez-Cadavid, N., Singh, A.B., Lee, M.I., et al. (2002). Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am. J. Physiol. Endocrinol. Metab. 283, E154-E164. doi: 10.1152/ajpendo.00502.2001.
139. Sinha-Hikim, I., Roth, S.M., Lee, M.I., and Bhasin, S. (2003). Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am. J. Physiol. Endocrinol. Metab. 285, E197-E205. doi: 10.1152/ajpendo.00370.2002.
140. Spanagel, R., Herz, A., and Shippenberg, T.S. (1992). Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U.S.A. 89, 2046-2050. doi: 10.1073/pnas.89.6.2046.
141. Steiner, H., and Gerfen, C.R. (1998). Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp. Brain Res. 123, 60-76. doi: 10.1007/s002210050545.
142. Tamaki, T., Shiraishi, T., Takeda, H., Matsumiya, T., Roy, R.R., and Edgerton, V.R. (2003). Nandrolone decanoate enhances hypothalamic biogenic amines in rats. Med. Sci. Sports Exerc. 35, 32-38. doi: 10.1097/00005768-200301000-00006.
143. Tanaka, K., Sakai, H., Hashizume, M., and Hirohata, T. (2000). Serum testosterone:estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients. Cancer Res. 60, 5106-5110.
144. Tennant, F., Black, D.L., and Voy, R.O. (1988). Anabolic steroid dependence with opioid-type features. N. Engl. J. Med. 319, 578. doi: 10.1056/NEJM198809013190910.
145. Thevis, M., Sauer, M., Geyer, H., Sigmund, G., Mareck, U., and Schänzer, W. (2008). Determination of the prevalence of anabolic steroids, stimulants, and selected drugs subject to doping controls among elite sport students using analytical chemistry. J. Sports Sci. 26, 1059-1065. doi: 10.1080/02640410801910293.
146. Thiblin, I., Finn, A., Ross, S.B., and Stenfors, C. (1999a). Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids. Br. J. Pharmacol. 126, 1301-1306. doi: 10.1038/sj.bjp.0702412.
147. Thiblin, I., Lindquist, O., and Rajs, J. (2000). Cause and manner of death among users of anabolic androgenic steroids. J. Forensic Sci. 45, 16-23.
148. Thiblin, I., Runeson, B., and Rajs, J. (1999b). Anabolic androgenic steroids and suicide. Ann. Clin. Psychiatry 11, 223-231. doi: 10.3109/10401239909147074.
149. Tremblay, M.S., Copeland, J.L., and Van Helder, W. (2004). Effect of training status and exercise mode on endogenous steroid hormones in men. J. Appl. Physiol. (1985) 96, 531-539. doi: 10.1152/japplphysiol.00656.2003.
150. Triemstra, J.L., Sato, S.M., and Wood, R.I. (2008). Testosterone and nucleus accumbens dopamine in the male Syrian hamster. Psychoneuroendocrinology 33, 386-394. doi: 10.1016/j.psyneuen.2007.12.006.
151. Tucci, P., Morgese, M.G., Colaianna, M., Zotti, M., Schiavone, S., Cuomo, V., et al. (2012). Neurochemical consequence of steroid abuse: stanozolol-induced monoaminergic changes. Steroids 77, 269-275. doi: 10.1016/j.steroids.2011.12.014.
152. van der Vegt, B.J., Lieuwes, N., van de Wall, E.H., Kato, K., Moya-Albiol, L., Martínez-Sanchis, S., et al. (2003). Activation of serotonergic neurotransmission during the performance of aggressive behavior in rats. Behav. Neurosci. 117, 667-674. doi: 10.1037/0735-7044.117.4.667.
153. Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Ding, Y.S., Sedler, M., et al. (2001a). Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am. J. Psychiatry 158, 2015-2021. doi: 10.1176/appi.ajp.158.12.2015.
154. Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Franceschi, D., Sedler, M., et al. (2001b). Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J. Neurosci. 21, 9414-9418.
155. Volkow, N.D., Fowler, J.S., Wolf, A.P., Schlyer, D., Shiue, C.Y., Alpert, R., et al. (1990). Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am. J. Psychiatry 147, 719-724. doi: 10.1176/ajp.147.6.719.
156. Wichstrom, L., and Pedersen, W. (2001). Use of anabolic-androgenic steroids in adolescence: winning, looking good or being bad? J. Stud. Alcohol 62, 5-13. doi: 10.15288/jsa.2001.62.5
157. Wines, J.D. Jr., Gruber, A.J., Pope, H.G. Jr., and Lukas, S.E. (1999). Nalbuphine hydrochloride dependence in anabolic steroid users. Am. J. Addict. 8, 161-164. doi: 10.1080/105504999305965.
158. Wood, R.I. (2002). Oral testosterone self-administration in male hamsters: dose-response, voluntary exercise, and individual differences. Horm. Behav. 41, 247-258. doi: 10.1006/hbeh.2002.1769.
159. Wood, R.I. (2004). Reinforcing aspects of androgens. Physiol. Behav. 83, 279-289. doi: 10.1016/j.physbeh.2004.08.012.
160. Wood, R.I. (2008). Anabolic-androgenic steroid dependence? Insights from animals and humans. Front. Neuroendocrinol. 29, 490-506. doi: 10.1016/j.yfrne.2007.12.002.
161. Wood, R.I., Johnson, L.R., Chu, L., Schad, C., and Self, D.W. (2004). Testosterone reinforcement: intravenous and intracerebroventricular self-administration in male rats and hamsters. Psychopharmacology (Berl) 171, 298-305. doi: 10.1007/s00213-003-1587-7.
162. Yates, W. (2000). Testosterone in psychiatry. Arch. Gen. Psychiatry 57, 155-156. doi: 10.1001/archpsyc.57.2.155
163. Yates, W.R., Perry, P.J., and Andersen, K.H. (1990). Illicit anabolic steroid use: a controlled personality study. Acta Psychiatry Scand. 81, 548-550. doi: 10.1111/j.1600-0447.1990.tb05496.x.
164. Yesalis, C.E., Bahrke, M.S., Kopstein, A.N., and Barsukiewicz, C.K. (2000). "Incidence of anabolic steroids use: a discussion of methodological issues," in Anabolic Steroids in Sport and Exercise, 2nd Edn., ed C. E. Yesalis (Champaign, IL: Human Kinetics), 73-115.
165. Zotti, M., Tucci, P., Colaianna, M., Morgese, M.G., Mhillaj, E., Schiavone, S., et al. (2014). Chronic nandrolone administration induces dysfunction of the reward pathway in rats. Steroids 79, 7-13. doi: 10.1016/j.steroids.2013.10.005.