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The endocannabinoid system is capable of modulating multiple physiological brain functions including learning and memory. Moreover, there is evidence that the processes of acquisition and consolidation have distinct biological basis. We used the cannabinoid agonist WIN 55,212-2 (WIN-2) to investigate whether chronic CB1 activation affects acquisition and consolidation differently by evaluating gene expression in the hippocampus (HIP) and prefrontal cortex (PFC). Swiss mice were treated with WIN-2 (2 mg/kg) and submitted to the Morris water maze to evaluate different aspects of memory. We observed short-term memory impairment in acquisition of the spatial task while consolidation remained unchanged. In the PFC, animals that received WIN-2 prior to the task exhibited increased expression of the 2-AG synthesis enzyme diacylglycerol lipase and decreased levels of the degradation enzyme monoacylglycerol lipase, while mice that were treated after the task for the evaluation of consolidation exhibited the opposite profile. With respect to genes related to AEA metabolism, no correlation between the molecular and behavioral data could be established. In this sense, the cognitive impairment in the acquisition promoted by WIN-2 treatment may be related to a possible increase in the concentration of 2-AG in the PFC. Overall, this study confirms the relevance of the endocannabinoid system in the modulation of cognitive processes. A better understanding of the mechanisms underlying endocannabinoids roles in cognition could provide guidance for the development of treatments to reduce the cognitive deficits caused by drug abuse., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)