The effect of tri-iodothyronine in combination with imipramine on [H]-cyclic AMP production in slices of rat cerebral cortex

Tri-iodothyronine (T₃; 15 μg) was administered to rats, alone or in combination with imipramine (20 mg/kg), for 5 days. The net synthesis of [³H]-cyclic AMP in cerebral cortex slices of animals so treated and control rats was then measured. The dose-dependent stimulation of [³H]-cyclic AMP by norepinephrine (NE) was significantly reduced in imipramine-treated rats. Tri-iodothyronine treatment had no effect on the enhanced net synthesis of [³H]-cyclic AMP produced by NE. In cortex slices of rats given both T₃ and imipramine, NE produced less stimulation of [³H]-cyclic AMP than in control rats. The magnitude of this inhibitory effect was less than that observed in animals treated with imipramine alone. In vitro addition of imipramine to the cortex slice preparation reduced the stimulation of [³H]-cyclic AMP caused by NE; treatment of rats with T₃ did not modify this inhibitory effect of imipramine in vitro. Isoproterenol produced significantly less stimulation of [³H]-cyclic AMP net synthesis than did NE; imipramine added in vitro had no effect on the stimulation produced by isoproterenol. It is concluded that the reason for the enhanced clinical effect of imipramine when given together with T₃ is not due to the hormone exaggerating the effect of the antidepressant on NE stimulated adenylate cyclase. Furthermore, for NE to produce maximal stimulation of [³H]-cyclic AMP, uptake of the catecholamine is necessary.