EXCITATION OF NORADRENERGIC CELL FIRING BY 5-HYDROXYTRYPTAMINE(1A) AGONISTS CORRELATES WITH DOPAMINE ANTAGONIST PROPERTIES

The 5-HT1A receptor agonists buspirone, 8-hydroxy-N,N-dipropyl-2-amino tetralin, gepirone and ipsapirone were evaluated for their receptor bi nding profiles and their effects on firing rates of 5-HT, dopamine (DA ) and noradrenaline (NA) neurons in the dorsal raphe, substantia nigra pars compacta and the locus ceruleus, respectively. All agents bound to 5-HT1A receptors with high affinities. All agents also bound to dop amine D2 receptors but, with the exception of buspirone, affinities we re usually much lower than for 5-HT1A receptors. All agents depressed 5-HT neurons, with 8-hydroxy-N,N-dipropyl-2-aminotetralin having a pot ency about 8 to 12 times those for the other three. All agents also an tagonized the inhibition of DA neurons by amphetamine, an index of DA antagonist properties. Buspirone reversed amphetamine's effects with d oses similar to those for depressing 5-HT neurons, but the remaining t hree required much higher doses to affect DA neuron function. All four 5-HT1A agonists excited NA neurons. In each case, doses required for excitation of NA cells were similar to those reversing amphetamine's e ffects on DA cells, but not to those for depressing 5-HT cells. Halope ridol also stimulated NA cells. It is concluded that excitation of NA neurons by 5-HT1A agonists may be due to interactions with dopaminergi c, rather than serotonergic, receptors.