Electrophysiological evidence that spiperone is an antagonist of 5-HT sub(1A) receptors in the dorsal raphe nucleus

The neuroleptic spiperone, which binds to 5-HT sub(1A), 5-HT sub(2) and dopamine (DA ) receptors, was studied for its effects on serotonin (5-HT) and DA neurons in dorsal raphe nucleus and substantia nigra pars compacta, respectively. It was found that spiperone, but not LY53837 (a 5-HT sub(2)) antagonist), antagonized the inhibition induced by 5-HT sub(1A) agonists 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and buspirone in the dorsal raphe nucleus. Lower spiperone doses blocked DA receptors in substantia nigra pars compacta, but did not affect 5-HT neurons. Doses of 8-OH-DPAT completely silencing dorsal raphe neurons were ineffective in substantia nigra pars compacta. However, buspirone antagonized DA receptors in substantia nigra pars compacta with doses similar to those depressing dorsal raphe neurons. It is concluded that spiperone is an antagonist of 5-HT sub(1A) receptors in the dorsal raphe nucleus.