Behavioral effects in adult rats of chronic prepubertal treatment with the cannabinoid receptor agonist WIN 55,212-2

Abstract

Human and animal studies provide evidence for vulnerable periods of brain development for deleterious effects of cannabinoids. We have recently shown that pubertal chronic cannabinoid treatment leads to long-lasting behavioral deficits, whereas a comparable treatment in adult rats did not affect the animals' behavior. In the present study we examined the effects of an identical chronic cannabinoid treatment in juvenile rats, just before the onset of puberty. Treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days throughout the prepubertal period (postnatal days 15-40) in juvenile rats. The rats received a total of 20 injections intraperitoneally. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity and prepulse inhibition (PPI) of the acoustic startle response. Juvenile chronic WIN administration had no effect on object recognition memory, PR performance and locomotor activity in adulthood. However, a PPI deficit was observed in WIN-treated rats when tested as adults that could be reversed by the acute administration of the dopamine receptor antagonist haloperidol (0.1 mg/kg). Additionally, juvenile cannabinoid treatment reduced the number of rearings, as well as the time spent in the center of the open field in adult rats, suggesting increased anxiety. Juvenile chronic cannabinoid treatment induced behavioral disturbances in adult rats that are less severe than those observed after pubertal cannabinoid administration. However, based on the observations of sensorimotor gating deficits and increased anxiety, we conclude that the prepubertal developmental phase, in addition to puberty, also represents a vulnerable time period for persistent adverse effects of cannabinoids.