GABAA receptor density is altered by cannabinoid treatment in the hippocampus of adult but not adolescent rats

Cannabinoids are known to induce transient psychotic symptoms and cognitive dysfunction in healthy individuals and contribute to trigger schizophrenia in vulnerable individuals, particularly during adolescence. Converging preclinical evidence suggests important interactions between cannabinoid and GABAergic systems. In the present study, we compared the effects of cannabinoid treatment on GABAA receptor binding in the brain of adolescent and adult rats. Adolescent (5 weeks old) and adult (10 weeks old) rats were treated with the synthetic cannabinoid HU210 (25, 50 or 100 μg/kg/day) or vehicle for 1, 4 or 14 days. Rats were sacrificed 24 h after the last injection and GABAA receptor density was measured in several brain regions using [35S]TBPS and in vitro autoradiography. Adolescent rats had higher numbers of GABAA receptors compared to adults. A 24% increase of binding in adult rats treated with 100μg/kg HU210 for 14 days compared to controls was observed in the CA1 region of the hippocampus (16.1 versus 12.9 fmol/mg tissue equivalent, t = 2.720, p < 0.05). HU210 did not affect GABAA receptors in adolescent rats in any treatment regimen and in adult rats treated with HU210 for 1 or 4 days. These data suggest that long-term, high-dose treatment with HU210 increases GABAA receptors in the hippocampus of adult rats, changes that may interfere with associated hippocampal cognitive functions such as learning and memory. In addition, our results suggest that the adolescent brain does not display the same compensatory mechanisms that are activated in the adult brain following cannabinoid treatment.