Electrophysiological evidence for postsynaptic 5-HT(1A) receptor control of dorsal raphe 5-HT neurones.

Postsynaptic 5-hydroxytryptamine(1A) (5-HT(1A)) receptors have been proposed to participate in the control of dorsal raphe 5-HT neurone activity. To further investigate this hypothesis we performed single-unit extracellular recordings in anaesthetized rats. Pertussis toxin (2 microg/4 microl/day; 2 days, 24-72 h before the experiment) was applied close to the dorsal raphe nucleus to uncouple somatodendritic 5-HT(1A) autoreceptors from their effector system. After this treatment the spontaneous firing rate was higher (approximately +60% P<0.005) than in the vehicle-pretreated group. In addition, intravenous administration of 8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) inhibited 5 out of 11 cells of the pertussis toxin-pretreated group (ED(50)=1.65+/-0.94 microg/kg), whereas in the vehicle-pretreated group, all tested cells were inhibited (ED(50)=1.87+/-0.39 microg/kg). Local administration of 8-OH-DPAT did not affect cells (n=12) in pertussis toxin-pretreated rats, even at doses much higher than those needed to completely inhibit 5-HT cells in vehicle-pretreated rats (ED(50)=3.34+/-0.62 fmol). These results confirm the involvement of distal postsynaptic 5-HT(1A) receptors in the control of 5-HT neurone activity in the dorsal raphe nucleus. However, this control does not appear to be exerted on all 5-HT neurones, but rather on a subpopulation of them.