Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats
British Journal of Pharmacology – November 15, 2013
Source: OpenAlex
Summary
Adolescent exposure to THC and MDMA leads to significant long-term neurochemical changes in male and female rats. In males, both drugs increased reactive microglia cells by 41%, while in females, MDMA reduced serotonin transporter (SERT) positive fibers by 25%. Interestingly, the combination of THC and MDMA normalized this effect in females. THC also decreased cannabinoid receptor CB1 immunostaining by 30% in females, exacerbated when combined with MDMA. These findings highlight the complex interplay between these substances and their sex-dependent effects on neuroinflammation and neurotransmitter systems.
Abstract
Background and Purpose Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long‐term effects of Δ 9 ‐tetrahydrocannabinol ( THC ) and 3,4‐methylenedioxymethamphetamine ( MDMA ) on diverse neuroinflammation and neurotoxic markers. Experimental Approach Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. Key Results THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 ( I ba‐1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a ‘normalization’ to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB 1 receptors in females and this effect was aggravated by the combination with MDMA . Conclusions and Implications Adolescent exposure of rats to THC and/or MDMA induced long‐term, sex‐dependent neurochemical and glial alterations, and revealed interactions between the two drugs. Linked Articles This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐6