AI Article Synopsis
- - Crack-cocaine addiction is a growing public health issue, particularly in developing countries, but research on its neurobiological mechanisms is lacking compared to powder cocaine.
- - A study on mice exposed to crack-cocaine showed increased movement and unique jumping behavior, with a focus on the biochemical effects on the dopamine and endocannabinoid systems in the prefrontal cortex.
- - Findings revealed higher levels of AEME, a metabolite specific to crack-cocaine, alongside downregulation of endocannabinoid-related genes and alterations in dopamine receptor activity, suggesting that prolonged exposure leads to significant neuroadaptive changes distinct from those seen with powder cocaine.
Article Abstract
Crack-cocaine addiction has increasingly become a public health problem worldwide, especially in developing countries. However, no studies have focused on neurobiological mechanisms underlying the severe addiction produced by this drug, which seems to differ from powder cocaine in many aspects. This study investigated behavioural, biochemical and molecular changes in mice inhaling crack-cocaine, focusing on dopaminergic and endocannabinoid systems in the prefrontal cortex. Mice were submitted to two inhalation sessions of crack-cocaine a day (crack-cocaine group) during 11 days, meanwhile the control group had no access to the drug. We found that the crack-cocaine group exhibited hyperlocomotion and a peculiar jumping behaviour ("escape jumping"). Blood collected right after the last inhalation session revealed that the anhydroecgonine methyl ester (AEME), a specific metabolite of cocaine pyrolysis, was much more concentrated than cocaine itself in the crack-cocaine group. Most genes related to the endocannabinoid system, CB1 receptor and cannabinoid degradation enzymes were downregulated after 11-day crack-cocaine exposition. These changes may have decreased dopamine and its metabolites levels, which in turn may be related with the extreme upregulation of dopamine receptors and tyrosine hydroxylase observed in the prefrontal cortex of these animals. Our data suggest that after 11 days of crack-cocaine exposure, neuroadaptive changes towards downregulation of reinforcing mechanisms may have taken place as a result of neurochemical changes observed on dopaminergic and endocannabinoid systems. Successive changes like these have never been described in cocaine hydrochloride models before, probably because AEME is only produced by cocaine pyrolysis and this metabolite may underlie the more aggressive pattern of addiction induced by crack-cocaine.
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| http://dx.doi.org/10.1016/j.bbr.2015.04.036 | DOI Listing |
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