Chronic treatment with CP 55,940 during the peri-adolescent period differentially affects the behavioural responses of male and female rats in adulthood

Despite the increasing use of cannabis among adolescents, there is scarce information about the long-term effects of cannabinoid receptor agonists in appropriate animal models. We aimed to investigate the behavioural features of adult male and female Wistar rats that had been exposed to a chronic treatment with the cannabinoid receptor agonist CP 55,940 (CP) during the juvenile period. CP (0.4 mg/kg i.p.) or its corresponding vehicle was administered once daily, from day 35 to day 45. In adulthood, the animals were tested in the holeboard, the open field and the elevated plus-maze, under different stress (illumination) conditions. After a resting period, the serum corticosterone levels (radioimmunoassay) of the animals were measured. The effects of CP on food intake and somatic growth were monitored throughout the experimental period. The CP treatment induced significant sex-dependent effects on holeboard activity, as well as a decrease in the level of emotionality/anxiety in the open field and in the plus-maze. The animals receiving CP also showed diminished food intake and body weights during the treatment period, but both parameters recovered normal values during the period after treatment. No significant effect of the CP treatment on corticosterone levels was found. The results demonstrate that chronic administration of CP during the peri-adolescent period resulted in marked behavioural effects in adulthood. The nature of these effects depended on the sex of the animals and on the specific behavioural test. The possible neurobiological substrates underlying the effects of CP are discussed.