The anticonvulsant activity of trace amine-associated receptor 1 (TAAR1) agonists involves GABAB receptors in mice

Trace amine-associated receptor 1 (TAAR1) agonists have shown potential as therapeutic agents for schizophrenia and other neuropsychiatric disorders. However, it remains unclear whether TAAR1 agonists have anticonvulsant activity. We therefore investigated the effects of TAAR1 agonists on acute seizures induced by continuous intravenous infusion of a GABA_A receptor antagonist, pentylenetetrazol (PTZ), and an inhibitor of voltage-gated potassium channels, 4-aminopyridine (4-AP), in mice. The TAAR1 agonists RO5263397 and RO5256390 did not affect the threshold dose for PTZ-induced seizures; however, they significantly increased the threshold for 4-AP-induced seizures. The anticonvulsant activities of these TAAR1 agonists were blocked by intracerebroventricular administration of CGP 35348, a GABA_B receptor antagonist. These results suggest that GABA_B receptors are involved in the anticonvulsant effects of TAAR1 agonists.