Cannabinoids and novelty investigation: Influence of age and duration of exposure

Administration of the synthetic cannabinoid receptor agonist WIN 55,212-2 has been shown to increase indices of noradrenergic activity. Neuroanatomical, neurochemical and behavioral studies have provided evidence supporting a marked impact of cannabinoids on the rat coeruleo-cortical pathway. As activity of this pathway is implicated in setting specific attentional modes, the present study assessed the influence of acute and repeated systemic administration of WIN 55,212-2 on novelty investigation in adolescent and adult male rats by using the hole board behavioral paradigm. Animals were individually acclimated to the hole board for 10-min sessions over 3 days, and novel objects were introduced on the fourth day. Novelty-seeking behavior was measured by comparison of the average number of return visits to a hole containing a novel object versus the average number of return visits to an empty hole. While attenuation of novelty preference was observed in adult rats acutely treated with WIN 55,212-2, both acutely treated adolescent groups retained their preference for novelty. All groups treated with repeated administration of either drug or vehicle demonstrated novelty preference, and no differences were found in the measure of novelty investigation between the groups. Furthermore, this study reproduced findings showing significant differences in locomotor activity that did not coincide with differences in novelty-seeking behavior. These data thus suggest a complex effect of CB1 receptor modulation on novelty preference in the male rat that is modulated by age and treatment.