The cannabinoid agonist WIN-2 affects acquisition but not consolidation of a spatial information in training and retraining processes: Relation with transcriptional regulation of the endocannabinoid system?

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.

The contribution of mild thiamine deficiency and ethanol consumption to central cholinergic parameter dysfunction and rats' open-field performance impairment.

We studied at the biochemical, morphological, and behavioral levels the effect of chronic ethanol consumption, associated or not with a mild thiamine deficiency episode. We found that (i) thiamine deficiency induced a significant decrease of the acetylcholinesterase (AChE) activity both in cortex and hippocampus; (ii) chronic ethanol treatment has no effect on cortical AChE activity, but induced a significant decrease of hippocampal enzyme activity; (iii) the reduction in cortical and hippocampal AChE activity induced by chronic ethanol treatment associated with a 1-week thiamine deficiency was also significant and was greater than that induced by ethanol alone. Furthermore, either chronic ethanol or thiamine deficiency induced a significant decrease in the release of acetylcholine (ACh) in the stimulated condition using high potassium concentration; and when both treatments were associated the decrease was even greater. In the unstimulated condition, the reduction in the release of ACh was greater for ethanol treatment than for thiamine deficiency. Open-field tests showed that only in the "sniffing" category were there significant differences among the experimental groups. No morphological change was detected by optical microscopy, suggesting that the injury process was in its initial stages in which only functional and behavioral changes are displayed. In addition, our biochemical results indicate that cortical cholinergic susceptibilities to ethanol and thiamine deficiency are significantly different.