Reduced sensitivity of neurons to noradrenamine after chronic treatment with antidepressant drugs

The sensitivity of cingulate cortical neurons to microiontophoretically administered noradrenaline (NE) and GABA was investigated in groups of rats treated either chronically or acutely with various antidepressant drugs or with the tricyclic antiepileptic carbamazepine. The chronically treated animals received one daily intraperitoneal injection of either desipramine (10 mg/kg), clomipramine (10 mg/kg), maprotiline (25 mg/kg), tranylcypromine (1 mg/kg) or carbamazepine (30 mg/kg p.o) for 4 weeks. The acutely treated rats received one daily injection of the vehicle for 4 weeks, followed by one single injection of one of the five drugs 24 h before the experiment. NE and γ-aminobutyric acid (GABA) were administered microiontophoretically during periods of 60 sec with various ejection currents. In chronically treated rats a statistically significant reduction in the sensitivity of cortical cells to NE was observed with all four antidepressants. However, in rats treated chronically with carbamazepine, no desensitisation was observed.Desensitization to NE following chronic treatment with desipramine developed within the first 10 days of treatment. Following a ten-day treatment, there was a 33 percent and by the end of the fourth week a 43 percent reduction in sensitivity to NE. The sensitivity of these cingulate neurons to GABA was unchanged after chronic treatment with the antidepressant drugs. In conclusion, the present study demonstrates that chronic treatment with antidepressant drugs leads to a postsynaptic subsensitivity of cortical neurons to NE.