Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects.
Maria Ellgren, A Artmann, O Tkalych, A Gupta, H S Hansen, S H Hansen, Lakshmi A Devi, Yasmin L. Hurd
European Neuropsychopharmacology November 2008 DOI: 10.1016/j.euroneuro.2008.06.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent rats |
| Intervention | Delta-9-tetrahydrocannabinol (THC) |
| Dose | 1.5 mg/kg i.p. every third day |
| Duration | From postnatal days 28 to 49, with examinations 24 h after injection at PND 29, 38, and 50 |
| Topics | Cannabis |
| Key findings | THC exposure during adolescence altered endocannabinoid and opioid markers in mesocorticolimbic regions, including reversed anandamide-2-arachidonoylglycerol correlations and increased anandamide with decreased Met-enkephalin and micro opioid receptors in the nucleus accumbens. |
Abstract
Adolescence is a critical phase of active brain development often characterized by the initiation of marijuana (Cannabis sativa) use. Limited information is known regarding the endogenous cannabinoid system of the adolescent brain as well as related neurotransmitters that appear sensitive to cannabis exposure. We recently observed that adult rats pre-exposed to Delta-9-tetrahydrocannabinol (THC) during adolescence self-administered higher amounts of heroin and had selective impairments of the enkephalin opioid system within the nucleus accumbens (NAc) implicated in reward-related behavior. To explore the ontogeny of the cannabinoid and opioid neuronal systems in association with adolescence THC exposure, rats were examined at different adolescent stages during an intermittent THC paradigm (1.5 mg/kg i.p. every third day) from postnatal days (PNDs) 28-49. Rat brains were examined 24 h after injection at PND 29 (early adolescence), PND 38 (mid adolescence) and PND 50 (late adolescence) and analyzed for endocannabinoids (anandamide and 2-arachidonoylglycerol), Met-enkephalin, cannabinoid CB(1) receptors and micro opioid receptors (microOR) in the NAc, caudate-putamen and prefrontal cortex (PFC). Of the markers studied, the endocannabinoid levels had the most robust alterations throughout adolescence and were specific to the PFC and NAc. Normal correlations between anandamide and 2-arachidonoylglycerol concentrations in the NAc (positive) and PFC (negative) were reversed by THC. Other significant THC-induced effects were confined to the NAc - increased anandamide, decreased Met-enkephalin and decreased microORs. These findings emphasize the dynamic nature of the mesocorticolimbic endocannabinoid system during adolescence and the selective mesocorticolimbic disturbance as a consequence of adolescent cannabis exposure.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Cannabis use before age 15 and subsequent executive functioning The British Journal of Psychiatry May 31, 2011
- Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness Frontiers in Psychiatry 2013
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia Translational Psychiatry November 27, 2012
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