Chronic periadolescent cannabinoid treatment enhances adult hippocampal PSA-NCAM expression in male Wistar rats but only has marginal effects on anxiety, learning and memory.

Pubertal and adolescent exposure to cannabinoids is associated with enduring alterations in anxiety and memory. However, periadolescence virtually remains unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP 55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p., 1 daily injection), and we also defined their recognition memory in the novel object paradigm and spatial learning and memory in the water maze. Additionally, we measured the expression of hippocampal PSA-NCAM (Polysialic Acid-Neural Cell Adhesion Molecule) and long-term potentiation (LTP) as well as, given their role in mnemonic processing, the levels of plasma corticosterone and estradiol. We found that CP had no robust effects on anxiety or in recognition memory. In the water maze, only a slight decreased percentage of failed trials in the reference memory task and an improvement in an indirect index of attention were observed. However, we detected an up-regulation of hippocampal PSA-NCAM expression, only in CP-males, although this effect was not related to changes in LTP. No hormonal alterations were evident. Based on our data, minimal long-term effects on anxiety, learning and memory appear to result from cannabinoid exposure during the periadolescent period.

Effects of medial prefrontal cortex and dorsal striatum lesions on retrieval processes in rats.

Exposure to training-related cues is known to reactivate associated memory and improves subsequent retention performance under various circumstances. The present studies investigated the neural basis of retrieval cue effects, by studying in two separate experiments, the involvement of the medial prefrontal cortex and of the dorsal striatum. Rats with lesions to the prelimbic-infralimbic cortex (PL-IL), to the anterior dorsal cingulate (ACd), and to the lateral and medial parts of the dorsal striatum (lDS and mDS) were first trained in a brightness discrimination avoidance task. One day later, rats were tested after being placed in the cueing box with either no training-related cue or with additional exposures to the light discriminative stimulus. None of the lesions affected the acquisition performance. During the retention test, control rats cued with the light in the box exhibited significantly better retention performance than those simply placed in the box, confirming our previous results. While mDS lesions did not modify effects of the retrieval cue, lDS as well as both PL-IL and ACd lesions blocked the facilitative effects of the discriminative stimulus. The present data indicate that ACd, PL-IL and lDS are involved in processes promoted by exposure to training cues, the nature of which are reviewed and discussed. This study in conjunction with previous ones suggests that retrieval cues activate several subcircuits mainly based on an amygdalo-prefrontal-striatum network. Activation of this network results in an improvement of the expression of the associated conditioned response, and may thus be viewed as increasing the efficacy of the retrieval processes.