Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats - PubMed

Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats

Maria Ellgren et al. Neuropsychopharmacology. 2007 Mar.

Abstract

Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 microg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 microg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 microg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

Similar articles

• Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood.

  Spano MS, Ellgren M, Wang X, Hurd YL. Spano MS, et al. Biol Psychiatry. 2007 Feb 15;61(4):554-63. doi: 10.1016/j.biopsych.2006.03.073. Epub 2006 Jul 28. Biol Psychiatry. 2007. PMID: 16876136

• Exposure to delta-9-tetrahydrocannabinol (THC) increases subsequent heroin taking but not heroin's reinforcing efficacy: a self-administration study in rats.

  Solinas M, Panlilio LV, Goldberg SR. Solinas M, et al. Neuropsychopharmacology. 2004 Jul;29(7):1301-11. doi: 10.1038/sj.npp.1300431. Neuropsychopharmacology. 2004. PMID: 15039767

• Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability.

  Tomasiewicz HC, Jacobs MM, Wilkinson MB, Wilson SP, Nestler EJ, Hurd YL. Tomasiewicz HC, et al. Biol Psychiatry. 2012 Nov 15;72(10):803-10. doi: 10.1016/j.biopsych.2012.04.026. Epub 2012 Jun 8. Biol Psychiatry. 2012. PMID: 22683090 Free PMC article.

• Animal evidence considered in determination of cannabis smoke and Δ⁹ -tetrahydrocannabinol (Δ⁹ -THC) as causing reproductive toxicity (developmental endpoint); Part II. Neurodevelopmental effects.

  Iyer P, Niknam Y, Campbell M, Moran F, Kaufman F, Kim A, Sandy M, Zeise L. Iyer P, et al. Birth Defects Res. 2022 Nov 1;114(18):1155-1168. doi: 10.1002/bdr2.2084. Epub 2022 Sep 16. Birth Defects Res. 2022. PMID: 36111653 Review.

• The consequences of neonatal pain, stress and opiate administration in animal models: An extensive meta-analysis concerning neuronal cell death, motor and behavioral outcomes.

  Steinbauer P, Monje FJ, Kothgassner O, Goreis A, Eva C, Wildner B, Schned H, Deindl P, Seki D, Berger A, Olischar M, Giordano V. Steinbauer P, et al. Neurosci Biobehav Rev. 2022 Jun;137:104661. doi: 10.1016/j.neubiorev.2022.104661. Epub 2022 Apr 12. Neurosci Biobehav Rev. 2022. PMID: 35427643 Review.

Cited by

• Trajectories of cannabis use and risk for opioid misuse in a young adult urban cohort.

  Reboussin BA, Rabinowitz JA, Thrul J, Maher B, Green KM, Ialongo NS. Reboussin BA, et al. Drug Alcohol Depend. 2020 Oct 1;215:108182. doi: 10.1016/j.drugalcdep.2020.108182. Epub 2020 Jul 23. Drug Alcohol Depend. 2020. PMID: 32745836 Free PMC article.

• Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake.

  Avena NM, Rada P, Hoebel BG. Avena NM, et al. Neurosci Biobehav Rev. 2008;32(1):20-39. doi: 10.1016/j.neubiorev.2007.04.019. Epub 2007 May 18. Neurosci Biobehav Rev. 2008. PMID: 17617461 Free PMC article. Review.

• Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait.

  Rodríguez-Arias M, Roger-Sánchez C, Vilanova I, Revert N, Manzanedo C, Miñarro J, Aguilar MA. Rodríguez-Arias M, et al. Neural Plast. 2016;2016:6481862. doi: 10.1155/2016/6481862. Epub 2015 Dec 31. Neural Plast. 2016. PMID: 26881125 Free PMC article.

• Persistent Exposure to Δ⁹-Tetrahydrocannabinol during Adolescence Does Not Affect Nociceptive Responding in Adult Mice.

  Mabou Tagne A, Fotio Y, Ibne Rashid T, Piomelli D. Mabou Tagne A, et al. J Pharmacol Exp Ther. 2021 Sep;378(3):215-221. doi: 10.1124/jpet.121.000740. Epub 2021 Jun 28. J Pharmacol Exp Ther. 2021. PMID: 34183435 Free PMC article.

• Interacting Cannabinoid and Opioid Receptors in the Nucleus Accumbens Core Control Adolescent Social Play.

  Manduca A, Lassalle O, Sepers M, Campolongo P, Cuomo V, Marsicano G, Kieffer B, Vanderschuren LJ, Trezza V, Manzoni OJ. Manduca A, et al. Front Behav Neurosci. 2016 Nov 16;10:211. doi: 10.3389/fnbeh.2016.00211. eCollection 2016. Front Behav Neurosci. 2016. PMID: 27899885 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program