Interactions between kappa opioid agonists and cocaine. Preclinical studies

Annals of the New York Academy of Sciences

Volumn 909, Issue , 2000, Pages 104-132

  Mello, Nancy K ^a   Negus, S Stevens ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZOMORPHAN; BREMAZOCINE; COCAINE; CYCLAZOCINE; DOPAMINE; ENADOLINE; KAPPA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR AGONIST; MU OPIATE RECEPTOR; NALOXONE; SPIRADOLINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; COCAINE DEPENDENCE; CONFERENCE PAPER; DISCRIMINATIVE STIMULUS; DOPAMINE RELEASE; DOPAMINERGIC NERVE CELL; LIMBIC CORTEX; NONHUMAN; RHESUS MONKEY; SEDATION; VOMITING;

ANIMALIA; EMESIS; MACACA MULATTA; RODENTIA;

EID: 0033929804     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2000.tb06678.x     Document Type: Conference Paper

References (94)

1. 1. ARCHER, S., S.D. GLICK & J. BIDLACK. 1996. Cyclazocine revisited. Neurochemical Res. 21: 1369-1373.
2. 2. NIDA Epidemiologic Trends in Drug Abuse. 1998. Volume 1: Highlights and Executive Summary. National Institute on Drug Abuse. Washington, D.C.
3. 3. MENDELSON, J.H. & N.K. MELLO. 1996. Drug therapy: management of cocaine abuse and dependence. N. Engl. J. Med. 334: 965-972.
4. 4. KOE, B.K. 1976. Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J. Pharmacol. Exp. Ther. 199: 649-661.
5. 5. REITH, M.E.A. 1988. Cocaine receptors on monoamine transporters and sodium channels. In Mechanisms of Cocaine Abuse and Toxicity. D. Clouet, K. Asghar & R. Brown, Eds. NIDA Res. Monogr. 88: 23-43.
6. 6. TAYLOR, D. & B.T. HO. 1978. Comparison of inhibition of monoamine uptake by cocaine, methylphenidate and amphetamine. Res. Commun. Chem. Pathol. Pharamcol. 21: 67-75.
7. 7. RITZ, M.C., R.J. LAMB, S.R. GOLDBERG & M.J. KUHAR. 1987. Cocaine receptors in dopamine transporters are related to self-administration of cocaine. Science 237: 1219-1223.
8. 8. KOOB, G.F. & F.E. BLOOM. 1988. Cellular and molecular mechanisms of drug dependence. Science 242: 715-723.
9. 9. JOHANSON, C.E. & M.W. FISCHMAN. 1989. The pharmacology of cocaine related to its abuse. Pharmacol. Rev. 41: 3-52.
10. 10. KUHAR, M.J., M.C. RITZ & J.W. BOJA. 1991. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci. 14: 299-302.
11. 11. WOOLVERTON, W.L. & K.M. JOHNSON. 1992. Neurobiology of cocaine abuse. Trends Pharmacol. Sci. 13: 193-200.
12. 12. MELLO, N.K. & S.S. NEGUS. 1996. Preclinical evaluation of pharmacotherapies for treatment of cocaine and opioid abuse using drug self-administration procedures. Neuropsychopharmacology 14: 375-424.
13. 13. KLEVEN, M.S. & W.L. WOOLVERTON. 1990. Effects of continuous infusions of SCH 23390 on cocaine-or food-maintained behavior in rhesus monkeys. Behav. Pharmacol. 1: 365-373.
14. 14. NEGUS, S.S., N.K. MELLO, X. LAMAS & J.H. MENDELSON. 1996. Acute and chronic effects of flupenthixol on the discriminative stimulus and reinforcing effects of cocaine in rhesus monkeys. J. Pharmacol. Exp. Ther. 278: 879-890.
15. 15. MANSOUR, A., H. KHACHATURIAN, M.E. LEWIS, H. AKIL & S.J. WATSON. 1987. Autoradiographic differentiation of mu, delta and kappa opioid receptors in rat forebrain and midbrain. J. Neurosci. 7: 2445-2464.
16. 16. MANSOUR, A., H. KHACHATURIAN, M.E. LEWIS, H. AKIL & S.J. WATSON. 1988. Anatomy of CNS opioid receptors. Trends Neurosci. 11: 308-314.
17. 17. MANSOUR, A., C.A. FOX, S. BURKE, F. MENG, R.C. THOMPSON, H. AKIL & S.J. WATSON. 1994. Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: An in situ hybridization study. J. Comp. Neurol. 350: 412-438.
18. 18. HOKFELT, T., S.R. VINCENT, C.J. DALSGAARD, M. HERRERA-MARSCHITZ, U. UNDERSTEDT, M. SCHULTZBERG, I. CHRISTENSSON & L. TERENIUS. 1984. Some aspects on distribution and role of opioid peptides in the central and peripheral nervous system. In Central and Peripheral Endorphins: Basic and Clinical Aspects. E.E. Muller & A.R. Genazzani, Eds. :1-16. Raven Press. New York.
19. 19. CHAVKIN, C., I.F. JAMES & A. GOLDSTEIN. 1982. Dynorphin is a specific endogenous ligand of the κ opioid receptor. Science 215: 413-415.
20. 20. DEVINE, D.P., P. LEONE, D. POCOCK & R.A. WISE. 1993. Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies. J. Pharmcol. Exp. Ther. 266: 1236-1246.
21. 21. DICHIARA, G. & A. IMPERATO. 1988. Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumens and in the dorsal caudate of freely moving rats. J. Pharmacol. Exp. Ther. 244: 1067-1080.
22. 22. DONZANTI, B.A., J.S. ALTHAUS, M.M. PAYSON & P.F. VONVOIGTLANDER. 1992. Kappa agonist-induced reduction in dopamine release: site of action and tolerance. Res. Commun. Chem. Pathol. Pharmacol. 78: 193-210.
23. 23. SPANAGEL, R., A. HERZ & T.S. SHIPPENBERG. 1992. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. USA 89: 2046-2050.
24. 24. MAISONNEUVE, I.M., S. ARCHER & S.D. GLICK. 1994. U50,488 a K opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens of rats. Neurosci. Lett. 181: 57-60.
25. 25. STEINER, H. & C.R. GERFEN. 1995. Dynorphin opioid inhibition of cocaine-induced, D1 dopamine receptor-mediated immediate-early gene expression in the striatum. J. Compar. Neurol. 353: 200-212.
26. 26. CRAWFORD, C.A., S.A. MCDOUGALL, C.A. BOLANOS, S. HALL & S.P. BERGER. 1995. The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immuoreactivity. Psychopharmacology 120: 392-399.
27. 27. HEIDBREDER, C.A., S. SCHENK, B. PARTRIDGE & T.S. SHIPPENBERG. 1998. Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to cocaine following repeated administration of a selective kappa-opioid agonist. Synapse 30: 255-262.
28. 2 receptors. Synapse 30: 275-283.
29. 29. HURD, Y.L. & M. HERKENHAM. 1993. Molecular alterations in the neostriatum of human cocaine addicts. Synapse 13: 357-369.
30. 30. UNTERWALD, E.M., J.M. RUBENFELD & M.J. KREEK. 1994. Repeated cocaine administration upregulates κ and μ but not δ, opioid receptors. NeuroReport 5: 1613-1616.
31. 2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. J. Neurosci. 17: 8225-8233.
32. 32. TURCHAN, J., B. PRZEWLOCKI, W. LASON & R. PRZEWLOCKI. 1998. Effects of repeated psychostimulant administration on the prodynorphin system activity and kappa opioid receptor density in the rat brain. Neuroscience 85: 1051-1059.
33. 33. DAUNAIS, J.B., D.C. ROBERTS & J.R. MCGINTY. 1995. Short-term cocaine self-administration alters striatal gene expression. Brain Res. Bull. 37: 523-527.
34. 34. DAUNAIS, J.B. & J.F. MCGINTY. 1995. Cocaine binges differentially alter striatal pre-prodynorphin and zif/268 mRNAs. Mol. Brain Res. 29: 201-210.
35. 35. HANSON, G.R., N. SINGH, K. MERCHANT, M. JOHNSON & W. GIBB. 1995. The role of NMDA receptor systems in neuropeptide responses to stimulants of abuse. Drug Alc. Depend. 37: 107-110.
36. 36. HYMAN, S.E. & E.J. NESTLER. 1996. Initiation and adaption: a paradigm for understanding psychotropic drug action. Am. J. Psychiatry 153: 151-162.
37. 37. UKAI, M., M. MIZUTANI & T. KAMEYAMA. 1994. Opioid peptides selective for receptor types modulate cocaine-induced behavioral responses in mice. Yakubutsu Seishin Kodo 14: 153-159.
38. 38. HEIDBREDER, C.A., D. BABOVIC-VUKSANOVIC, M. SHOAIB & T. SHIPPENBERG. 1995. Development of behavioral sensitization to cocaine: influence of kappa opioid receptor agonists. J. Pharmacol. Exp. Ther. 275: 150-163.
39. 39. SHIPPENBERG, T.S., A. LEFEVOUR & C.H. HEIDBREDER. 1996. κ-Opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine. J. Pharmacol. Exp. 276: 545-554.
40. 40. SUZUKI, T., Y. SHIOZAKI, Y. MASUKAWA, M. MISAWA & H. NAGASE. 1992. The role of mu-and kappa-opioid receptors in cocaine-induced conditioned place preference. Japan J. Pharmacol. 58: 435-442.
41. 41. SPEALMAN, R.D. & J. BERGMAN. 1992. Modulation of the discriminative stimulus effects of cocaine by mu and kappa opioids. J. Pharmacol. Exp. Ther. 261: 607-615.
42. 42. SPEALMAN, R.D. & J. BERGMAN. 1994. Opioid modulation of the discriminative stimulus effects of cocaine: comparison of μ, κ and δ agonists in squirrel monkeys discriminating low doses of cocaine. Behav. Pharmacol. 5: 21-31.
43. 43. BROADBENT, J., T.M. GASPARD & S.I. DWORKIN. 1995. Assessment of the discriminative stimulus effects of cocaine in the rat: lack of interaction with opioids. Pharmacol. Biochem. Behav. 51: 379-385.
44. 44. WOOLFOLK, D.R. & S.G. HOLTZMAN. 1997. μ-, κ-and δ-opioid receptor agonists do not alter the discriminative stimulus effects of cocaine or d-amphetamine in rats. Drug Alc. Depend. 48: 209-220.
45. 45. GLICK, S. D., I.M. MAISONNEUVE, J. RAUCCI & S. ARCHER. 1995. Kappa opioid inhibition of morphine and cocaine self-administration in rats. Brain Res. 681: 147-152.
46. 46. PORTOGHESE, P.S., A.W. LIPKOWSKI & A.E. TAKEMORI. 1987. Binaltorphimine and norbinaltorphimine, potent and selective kappa opioid receptor antagonists. Life Sci. 40: 1287-1292.
47. 47. KUZMIN, A.V., S. SEMENOVA, M.A.F.M. GERRITS, E.E. ZVARTAU & J.M. VAN REE. 1997. Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice. Eur. J. Pharmacol. 321: 265-271.
48. 48. BROADBEAR, J.H., S.S. NEGUS, E.R. BUTELMAN, B.R. DE COSTA & J.H. WOODS. 1994. Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on κ-opioid agonists in the mouse writhing assay. Psychopharmacology 115: 311-319.
49. 49. BUTELMAN, E.R., S.S. NEGUS, Y. AI, B.R. DE COSTA & J.H. WOODS. 1993. Kappa opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) in a thermal antinociception assay in rhesus monkeys. J. Pharmacol. Exp. Ther. 257: 1269-1276.
50. 50. JAFFE, J.H. & L. BRILL. 1966. Cyclazocine, a long acting narcotic antagonist: its voluntary acceptance as a treatment modality by narcotic abusers. Int. J. Addiction 1: 99-123.
51. 51. MARTIN, W R., H.F. FRASER, C.W. GORODETZKY & D.E. ROSENBERG. 1965. Studies of the dependence-producing potential of the narcotic antagonists 2-cyclopropylmethyl 2′-hydroxy-5,9-dimethyl-6,7-benzomorphan (cyclazocine, Win 20,740, ARC 11-C-3). J. Pharmacol. Exp. Ther. 150: 426-436.
52. 52. PFEIFFER, A., V. BRANTI, A. HERZ & H.M. EMRICH. 1986. Psychotomimesis mediated by κ opiate receptors. Science 233: 774-776.
53. 53. REECE, P.A., A.J. SEDMAN, S. ROSE, D.S. WRIGHT, R. DAWKINS & R. RAJAGOPALAN. 1994. Diuretic effects, pharmacokinetics, and safety of a new centrally acting kappa-opioid agonist (CI-977) in humans. J. Clin. Pharmacol. 34: 1126-1132.
54. 54. RIMOY, G.H., N.K. BHASKAR, D.M. WRIGHT & P.C. RUBIN. 1991. Mechanism of diuretic action of spiradoline (U-62066E) - a kappa opioid receptor agonist in the human. J. Clin. Pharmacol. 32: 611-615.
55. 55. BRANDT, M.R. & C.P. FRANCE. 1996. Discriminative stimulus effects of enadoline in pigeons. J. Pharmacol. Exp. Ther. 277: 960-967.
56. 56. DYKSTRA, L.A., D.E. GMEREK, G. WINGER & J.H. WOODS. 1987. Kappa opioids in rhesus monkeys. 1. Diuresis, sedation, analgesia and discriminative stimulus effects. J. Pharmacol. Exp. Ther. 242: 413-420.
57. 57. FRANCE, C.P., F. MEDZIHRADSKY & J.H. WOODS. 1994. Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities. J. Pharmacol. Exp. Ther. 268: 47-58.
58. 58. SMITH, M.A. & M.J. PICKER. 1995. Examination of the kappa agonist and antagonist properties of opioids in the rat drug discrimination procedure: influence of training dose and intrinsic efficacy. Behav. Pharmacol. 6: 703-717.
59. 59. EMMERSON, P.J., M.-R. LIU, J.H. WOODS & F. MEDZIHRADSKY. 1994. Binding affinity and selecivity of opioids at mu, delta and kappa receptors in monkey brain membranes. J. Pharmacol. Exp. Ther. 271: 1630-1637.
60. 60. MAGNAN, J., S.J. PATERSON, A. TAVANI & H.W. KOSTERLITZ. 1982. The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn-Schmiedeberg's Arch. Pharmacol. 319: 197-205.
61. 61. WOOD, P.L. 1982. Multiple opiate receptors: support for unique mu, delta and kappa sites. Neuropsychopharmacology 21: 487-497.
62. 62. MILLER, L., J.S. SHAW & E.M. WHITING. 1986. The contribution of intrinsic activity to the action of opioids in vitro. Br. J. Pharmacol. 87: 595-601.
63. 63. REMMERS, A.E., M.J. CLARK, A. MANSOUR, H. AKIL, J.H. WOODS & F. MEDZIHRADSKY. 1999. Opioid efficacy in a C6 glioma cell line stably expressing the human kappa opioid receptor. J. Pharmacol. Exp. Ther. 288: 827-833.
64. 64. NOCK, B., A.L. GIORDANO, T.J. CICERO & L.H. O'CONOR. 1990. Affinity of drugs and peptides for U69,593-sensitive and -insensitive kappa opiate binding sites: the U69,593-insensitive site appears to be the beta endorphin specific epsilon receptor. J. Pharmacol. Exp. Ther. 254: 412-419.
65. 65. ROTHMAN R.B., V. BYKOV, B.R. DECOSTA, A.E. JACOBSON, K.C. RICE & L.S. BRADY. 1990. Interaction of endogenous opioid peptides and other drugs with four kappa opioid binding sites in guinea pig brain. Peptides 11: 311-331.
66. 66. SU, T.P. 1985. Further demonstration of kappa opioid binding sites in the brain: evidence for heterogeneity. J. Pharmacol. Exp. Ther. 232: 144-148.
67. 2 opioid receptors. Proc. Natl. Acad. Sci. USA 85: 4061-4065.
68. 68. BUTELMAN, E.R., C.P. FRANCE & J.H. WOODS. 1995. Agonist and antagonist effects of dynorphin A-(1-13) in a thermal antinociception assay in rhesus monkeys. J. Pharmacol. Exp. Ther. 275: 374-380.
69. 69. BUTELMAN, E.R., M.-C. KO, K. SOBCZYK-KOJIRO, H.I. MOSBERG, B. VAN BEMMEL, G. ZERNIG & J.H. WOODS. 1998. Kappa-opioid receptor binding populations in rhesus monkey brain: relationship to an assay of thermal antinociception. J. Pharmacol. Exp. Ther. 285: 595-601.
70. 2 analysis in rhesus monkeys. J. Pharmacol. Exp. Ther. 285: 518-526.
71. 71. NEGUS, S.S., N.K. MELLO, P.S. PORTOGHESE & C.-E. LIN. 1997. Effects of kappa opioids on cocaine self-administration by rhesus monkeys. J. Pharmacol. Exp. Ther. 282: 44-55.
72. 72. MELLO, N.K. & S.S. NEGUS. 1998. Effects of kappa opioid agonists on cocaine-and food-maintained responding by rhesus monkeys. J. Pharmacol. Exp. Ther. 286: 812-824.
73. 73. GATCH, M.B., S.S. NEGUS, N.K. MELLO, S. ARCHER & J.M. BIDLACK. 1996. Effects of the structurally novel opioid 14 α, 14′ β-[Dithiobis [(2-oxo-2, 1-ethanediyl)imino]]bis(7,8-dihydromorphinone) on schedule-controlled behavior and thermal nociception in rhesus monkeys. J. Pharmacol. Exp. Ther. 278: 1282-1289.
74. 74. NEGUS, S.S., T.F. BURKE, F. MEDZIHRADSKY & J.H. WOODS. 1993. Effects of opioid agonists selective for mu, kappa and delta opioid receptors on schedule-controlled responding in rhesus monkeys: antagonism by quadazocine. J. Pharmacol. Exp. Ther. 267: 896-903.
75. 75. NEGUS, S.S., E.R. BUTELMAN, K.J. CHANG, B.R. DECOSTA, G. WINGER & J.H. WOOD. 1994. Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys. J. Pharmacol. Exp. Ther. 270: 1025-1034.
76. 76. JONES, D.N.C. & S.G. HOLTZMAN. 1992. Long term κ-opioid receptor blockade following nor-binaltorphimine. Eur. J. Pharmacol. 215: 325-348.
77. 77. DAUNAIS, J.B. & J.F. MCGINTY. 1994. Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs. Synapse 18: 35-45.
78. 78. FRANCE, C.P., B.R. DECOSTA, A.E. JACOBSON, K.C. RICE & J.H. WOODS. 1990. Apparent affinity of opioid antagonists in morphine-treated rhesus monkeys discriminating between saline and naltrexone. J. Pharmacol. Exp. Ther. 252: 600-604.
79. 79. DAVIS, R.E., M.J. CALLAHAN, M. DICKERSON & D.A. DOWNS. 1992. Pharmacologic activity of CI-977, a selective kappa opioid agonist, in rhesus monkeys. J. Pharmacol. Exp. Ther. 261: 1044-1049.
80. 80. TAKEMORI, A.E., M.M. SCHWARTZ & P.S. PORTOGHESE. 1988. Suppression by norbinaltorphimine of kappa opioid-mediated diuresis in rats. J. Pharmacol. Exp. Ther. 247:971-974.
81. 81. GMEREK, D.E., L.A. DYKSTRA & J.H. WOODS. 1987. Kappa opioids in rhesus monkeys. III. Dependence associated with chronic administration. J. Pharmacol. Exp. Ther. 242: 428-436.
82. 82. BUTELMAN, E.R., C.P. FRANCE & J.H. WOODS. 1993. Apparent pA2 analysis of the respiratory depressant effects of alfentanil, etonitazene, ethylketocyclazocine (EKC) and Mr2033 in rhesus monkeys. J. Pharmacol. Exp. Ther. 264: 145-151.
83. 83. WOODS, J.H. & C.R. SCHUSTER. 1971. Opiates as reinforcing stimuli. In Stimulus Properties of Drugs. T. Thompson & R. Pickens, Eds. :163-175. Apple-Century-Crofts. New York.
84. 84. KILLIAN, A.K., K. BONESE & C.R. SCHUSTER. 1978. The effects of naloxone on behavior maintained by cocaine and heroin injections in the rhesus monkey. Drug Alc. Depend. 3: 243-251.
85. 85. COLPAERT, F.C., C.J.E. NIEMEGEERS & P.A.J. JANSSEN. 1979. Discriminative stimulus properties of cocaine: neuropharmacological characteristics as derived from stimulus generalization experiments. Pharmacol. Biochem. Behav. 10: 535-546.
86. 86. KLEVEN, M.S., E.W. ANTHONY & W.L. WOOLVERTON. 1990. Pharmacological characterization of the discriminative stimulus effects of cocaine in rhesus monkeys. J. Pharmacol. Exp. Ther. 254: 312-317.
87. 87. SPEALMAN, R.D., J. BERGMAN, B.K. MADRAS & K.F. MELIA. 1991. Discriminative-stimulus effects of cocaine in squirrel monkeys: involvement of dopamine receptor subtypes. J. Pharmacol. Exp. Ther. 258: 945-953.
88. 88. SUZUKI, T., T. MORI, M. TSUJI, J. MAEDA, Y. KISHIMOTO, M. MISAWA & H. NAGASE. 1997. Differential effects of mu-, delta-and kappa-opioid receptor agonists on the discriminative stimulus properties of cocaine in rats. Eur. J. Pharmacol 324: 21-29.
89. 89. NEGUS, S.S. & N.K. MELLO. 1999. Effects of kappa opioid agonists on the discriminative stimulus effects of cocaine in rhesus monkeys. Exp. Clin. Psychopharm. In press.
90. 3 receptor agonists partially reproduce the discriminative stimulus effects of cocaine in squirrel monkeys. J. Pharmacol. Exp. Ther. 278: 1128-1137.
91. 91. MARTIN, W.R., C.W. GORODETZKY & T.K. MCCLANE. 1966. An experimental study in the treatment of narcotic addicts with cyclazocine. Clin. Pharmacol. Ther. 455-464.
92. 92. WALSH, S.L., E.C. STRAIN, M.E. ABREU & G.E. BIGELOW. 1999. Pharmacodynamic profile of enadoline, a selective kappa (κ) agonist, in humans. In Problems of Drug Dependence, 1998. L.S. Harris, Ed. NIDA Res. Monogr. 179: 62. NIH Publ. No. 199-4395. U.S. Department of Health and Human Services, National Institutes of Health, Bethesda, MD.
93. 93. FOLTIN, R.W. & M.W. FISCHMAN. 1992. Self-administration of cocaine by humans: choice between smoked and intravenous cocaine. J. Pharmacol. Exp. Ther. 231: 841-849.
94. 94. POWELL, K.R. & S.G. HOLTZMAN. 1999. Modulation of the discriminative stimulus effects of d-amphetamine by mu and kappa opioids in squirrel monkeys. Pharmacol. Biochem. Behav. In press.