Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway

Neuropsychopharmacology

Volumn 43, Issue 10, 2018, Pages 2028-2035

  Ibarra Lecue, Inés ^a   Mollinedo Gajate, Irene ^a   Meana, J Javier ^a,b   Callado, Luis F ^a,b   Diez Alarcia, Rebeca ^a,b   Urigüen, Leyre ^a,b  

^a UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^b BIOCRUCES BIZKAIA HEALTH RESEARCH INSTITUTE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CANNABIS; DRONABINOL; G ALPHA I 1 PROTEIN; G ALPHA I 3 PROTEIN; G ALPHA O PROTEIN; G ALPHA Z PROTEIN; GUANINE NUCLEOTIDE BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE B; PSYCHEDELIC AGENT; RAPAMYCIN; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG; 4-IODO-2,5-DIMETHOXYPHENYLISOPROPYLAMINE; AMPHETAMINE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; MTOR PROTEIN, MOUSE; ONCOPROTEIN; SEROTONIN AGONIST; TARGET OF RAPAMYCIN KINASE;

AKT/MTOR SIGNALING; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; IN VITRO STUDY; IN VIVO STUDY; LONG TERM EXPOSURE; MALE; MOUSE; NONHUMAN; PREPULSE INHIBITION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; SCHIZOPHRENIA; SUPERSENSITIVITY; ANIMAL; BRAIN CHEMISTRY; DRUG EFFECT; METABOLISM; PSYCHOLOGY; SIGNAL TRANSDUCTION; STARTLE REFLEX;

AMPHETAMINES; ANIMALS; BRAIN CHEMISTRY; DRONABINOL; HALLUCINOGENS; MALE; MICE; ONCOGENE PROTEIN V-AKT; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTORS, G-PROTEIN-COUPLED; REFLEX, STARTLE; SCHIZOPHRENIC PSYCHOLOGY; SEROTONIN RECEPTOR AGONISTS; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 85046777352     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/s41386-018-0076-y     Document Type: Article

References (50)

1. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002;325:1212–3
2. Di Forti M, Marconi A, Carra E, Fraietta S, Trotta A, Bonomo M, et al. Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. Lancet Psychiatry. 2015;2:233–8
3. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374:1383–91
4. Foti DJ, Kotov R, Guey LT, Bromet EJ. Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalization. Am J Psychiatry. 2010;167:987–93
5. Nichols DE. Psychedelics. Pharmacol Rev. 2016;68:264–355
6. Gonzalez-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, et al. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron. 2007;53:439–52
7. Abdolmaleky HM, Yaqubi S, Papageorgis P, Lambert AW, Ozturk S, Sivaraman V, et al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr Res. 2011;129:183–90
8. Malkova NV, Gallagher JJ, Yu CZ, Jacobs RE, Patterson PH. Manganese-enhanced magnetic resonance imaging reveals increased DOI-induced brain activity in a mouse model of schizophrenia. Proc Natl Acad Sci USA. 2014;111:E2492–500
9. Santini MA, Ratner C, Aznar S, Klein AB, Knudsen GM, Mikkelsen JD. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia. J Neurosci Res. 2013;91:634–41
10. Muguruza C, Moreno JL, Umali A, Callado LF, Meana JJ, Gonzalez-Maeso J. Dysregulated 5-HT(2A) receptor binding in postmortem frontal cortex of schizophrenic subjects. Eur Neuropsychopharmacol. 2013;23:852–64
11. Grider MH, Park D, Spencer DM, Shine HD. Lipid raft-targeted Akt promotes axonal branching and growth cone expansion via mTOR and Rac1, respectively. J Neurosci Res. 2009;87:3033–42
12. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet. 2004;36:131–7
13. Gururajan A, van den Buuse M. Is the mTOR-signalling cascade disrupted in Schizophrenia? J Neurochem. 2014;129:377–87
14. Morgan CJ, Freeman TP, Powell J, Curran HV. AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. Transl Psychiatry. 2016;6:e738
15. Puighermanal E, Busquets-Garcia A, Gomis-González M, Marsicano G, Maldonado R, Ozaita A. Dissociation of the pharmacological effects of THC by mTOR blockade. Neuropsychopharmacol. 2013;38:1334–43
16. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008;118:3065–74
17. Kurita M, Holloway T, García-Bea A, Kozlenkov A, Friedman AK, Moreno JL, et al. HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nat Neurosci. 2012;15:1245–54
18. Diez-Alarcia R, Ibarra-Lecue I, Lopez-Cardona AP, Meana J, Gutierrez-Adan A, Callado LF, et al. Biased agonism of three different cannabinoid receptor agonists in mouse brain cortex. Front Pharmacol. 2016;7:415
19. Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 2008;452:93–97
20. Powell SB, Zhou X, Geyer MA. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009;204:282–94
21. Swerdlow NR, Braff DL, Taaid N, Geyer MA. Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry. 1994;51:139–54
22. Long LE, Chesworth R, Huang XF, McGregor IS, Arnold JC, Karl T. Transmembrane domain Nrg1 mutant mice show altered susceptibility to the neurobehavioural actions of repeated THC exposure in adolescence. Int J Neuropsychopharmacol. 2013;16:163–75
23. Aira Z, Buesa I, Garcia del Cano G, Salgueiro M, Mendiable N, Mingo J, et al. Selective impairment of spinal mu-opioid receptor mechanism by plasticity of serotonergic facilitation mediated by 5-HT2A and 5-HT2B receptors. Pain. 2012;153:1418–25
24. Rubino T, Parolaro D. The impact of exposure to cannabinoids in adolescence: insights from animal models. Biol Psychiatry. 2016;79:578–85
25. Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry. 1990;47:181–8
26. Ludewig K, Geyer MA, Vollenweider FX. Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry. 2003;54:121–8
27. Halberstadt AL, Geyer MA. Effect of Hallucinogens on Unconditioned Behavior. Current Topics in BehavioralNeurosciences. Berlin, Heidelberg: Springer; 2016. p. 1–41
28. Silva L, Black R, Michaelides M, Hurd YL, Dow-Edwards D. Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal. Neurotoxicol Teratol. 2016;58:88–100
29. Klein J, Hadar R, Gotz T, Manner A, Eberhardt C, Baldassarri J, et al. Mapping brain regions in which deep brain stimulation affects schizophrenia-like behavior in two rat models of schizophrenia. Brain Stimul. 2013;6:490–9
30. Schneider M, Koch M. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology. 2003;28:1760–9
31. Llorente-Berzal A, Fuentes S, Gagliano H, Lopez-Gallardo M, Armario A, Viveros MP, et al. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour. Addict Biol. 2011;16:624–37
32. Bortolato M, Aru GN, Frau R, Orru M, Luckey GC, Boi G, et al. The CB receptor agonist WIN 55,212-2 fails to elicit disruption of prepulse inhibition of the startle in Sprague- Dawley rats. Psychopharmacology. 2005;177:264–71
33. Galindo L, Moreno E, Lopez-Armenta F, Guinart D, Cuenca-Royo A, Izquierdo-Serra M, et al. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells. Mol Neurobiol. 2018; 10.1007/s12035-017-0833-7
34. Hill MN, Sun JC, Tse MT, Gorzalka BB. Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment. Int J Neuropsychopharmacol. 2006;9:277–86
35. Darmani NA. Cannabinoids of diverse structure inhibit two DOI-induced 5-HT(2A) receptor-mediated behaviors in mice. Pharmacol Biochem Behav. 2001;68:311–7
36. Nagai H, Egashira N, Sano K, Ogata A, Mizuki A, Mishima K, et al. Antipsychotics improve Delta9-tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice. Pharmacol Biochem Behav. 2006;84:330–6
37. Berk M, Brook S, Trandafir AI. A comparison of olanzapine with haloperidol in cannabis- induced psychotic disorder: a double-blind randomized controlled trial. Int Clin Psychopharmacol. 1999;14:177–80
38. de Oliveira RP, Nagaishi KY, Barbosa Silva RC. Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection ofDOI into the inferior colliculus in rats. Behav Brain Res. 2017;325:72–78
39. Farid M, Martinez ZA, Geyer MA, Swerdlow NR. Regulation of sensorimotor gating of the startle reflex by serotonin 2A receptors. Ontogeny and strain differences. Neuropsychopharmacology. 2000;23:623–32
40. De Lean A, Stadel JM, Lefkowitz RJ. A ternary complex model explains the agonist specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem. 1980;255:7108–17
41. Franklin JM, Carrasco GA. Cannabinoid-induced enhanced interaction and protein levels of serotonin 5-HT(2A) and dopamine D(2) receptors in rat prefrontal cortex. J Psychopharmacol. 2012;26:1333–47
42. Dowie MJ, Howard ML, Nicholson LF, Faull RL, Hannan AJ, Glass M. Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington’s disease transgenic mice. Neuroscience. 2010;170:324–36
43. Kurrasch-Orbaugh DM, Watts VJ, Barker EL, Nichols DE. Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. J Pharmacol Exp Ther. 2003;304:229–37
44. Gonzalez-Maeso J, Yuen T, Ebersole BJ, Wurmbach E, Lira A, Zhou M, et al. Transcriptome fingerprints distinguish hallucinogenic and nonhallucinogenic 5- hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex. J Neurosci. 2003;23:8836–43
45. Meana J, Miranda-Azpiazu P, Garcia-Bea A, Muguruza C, Callado L, Gabilondo A, et al. Selective up-regulation of serotonin 5-HT2A receptor coupling to G alpha(i1)-proteins in postmortem brain of subjects with schizophrenia. Eur Neuropsychopharmacol. 2014;24:S483–4
46. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124:471–84
47. Li J, Kim SG, Blenis J. Rapamycin: one drug, many effects. Cell Metab. 2014;19:373–9
48. Di Forti M, Iyegbe C, Sallis H, Kolliakou A, Falcone MA, Paparelli A, et al. Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol Psychiatry. 2012;72:811–6
49. van Winkel R, Genetic R, Outcome of Psychosis I. Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Arch Gen Psychiatry. 2011;68:148–57
50. Strachan RT, Sciaky N, Cronan MR, Kroeze WK, Roth BL. Genetic deletion of p90 ribosomal S6 kinase 2 alters patterns of 5-hydroxytryptamine 2A serotonin receptor functional selectivity. Mol Pharmacol. 2010;77:327–38