Effect of antidepressants on GABA(B) receptor function and subunit expression in rat hippocampus

Laboratory and clinical studies suggest that depression is associated with changes in the hippocampus and that this brain region is a major target for antidepressant drugs. Given the data suggesting that GABA(B) receptor antagonists display antidepressant properties, the present study was undertaken to assess the effect of antidepressant administration on GABA(B) receptors in the rat hippocampus to determine whether changes in this regional receptor system may play a role in the response to these agents. Rats were administered (i.p.) the monoamine oxidase inhibitors tranylcypromine (10mg/kg) or phenelzine (10mg/kg), the tricyclic antidepressant desipramine (15 mg/kg), or fluoxetine (5mg/kg), a selective serotonin re-uptake inhibitor, once daily for seven consecutive days. Two hours following the last drug treatment the hippocampal tissue was prepared for defining the distribution and quantity of GABA(B) receptor subunits using in situ hybridization and for assessing GABA(B) receptor function by quantifying baclofen-stimulated [(35)S]-GTPgammaS binding. All of these antidepressants selectively increased the expression of the GABA(B(1a)) subunit in hippocampus, having no consistent effect on the expression of GABA(B(1b)) or GABA(B(2)). Moreover, except for fluoxetine, these treatments increased GABA(B) receptor function in this brain region. The results indicate that an enhancement in the production of hippocampal GABA(B(1a)) subunits may be a component of the response to antidepressants, supporting a possible role for this receptor in the symptoms of depression and the treatment of this condition.