Electrophysiological evidence for postsynaptic 5-HT1A receptor control of dorsal raphe 5-HT neurones

Postsynaptic 5-hydroxytryptamine(1A) (5-HT1A) 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 mug/4 mul/day; 2 days, 24-72 h before the experiment) was applied close to the dorsal raphe nucleus to uncouple somatodendritic 5-HT1A autoreceptors from their effector system. After this treatment the spontaneous firing rate was higher (similar to +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 (ED50=1.65<plus/minus>0.94 mug/kg), whereas in the vehicle-pretreated group, all tested cells were inhibited (ED50=1.87 +/-0.39 mug/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 (ED50=3.34 +/-0.62 fmol). These results confirm the involvement of distal postsynaptic 5-HT1A 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. (C) 2001 Elsevier Science Ltd. All rights reserved.