EFFECTS OF AMITRIPTYLINE ON GABA-STIMULATED CL-36(-) UPTAKE IN RELATION TO A BEHAVIORAL-MODEL OF DEPRESSION

The dominant-submissive relationship established between two rats comp eting for food is a model of depression and is used here to divide ani mals into two behaviorally distinct groups. Basal and GABA-stimulated Cl-36(-) uptake was investigated for both dominant and submissive rats as well as the in vitro effect of the antidepressant amitriptyline (A MI). Because the antidepressant action of AMI only appears after chron ic treatment, the effect of chronic injections of AMI on these behavio ral and biochemical measures was also studied. Basal Cl-36(-) uptake i s significantly higher for dominant rats than for submissive rats. Inc reasing concentrations of AMI added to membrane vesicles enhanced 30 m u M GABA-stimulated chloride uptake for dominant rats and inhibited it for submissive rats. Chronic treatment of dominant and submissive rat s with AMI reversed these in vitro effects. The biochemical data corre spond to the changes of the rats behavior in the dominance test after chronic treatment with AMI. However, this correlation is more clear fo r dominant than for submissive rats. Specific chloride influx was used as a measure of the sensitivity of GABA(A) receptor to GABA. This rev ealed different sensitivity states for GABA(A) receptors in tissues ob tained from dominant and submissive rats. It is possible that the dist inct conformational states of GABA(A) receptor are responsible for dif ferences in rats behavior and in vitro effects of AMI before and after in vivo treatment of rats with this antidepressant.