Role of cholinergic and GABAergic systems in the feedback inhibition of dorsal raphe 5-HT neurons.
Several observations indicate that 5-HT1A receptors found on a long neuronal feedback loop, originating from the medial prefrontal cortex, regulate 5-HT neuronal firing. In the present study, the muscarinic (M) receptor antagonists atropine and scopolamine as well as the M2 receptor antagonist AF-DX 116, but not the preferential M1 receptor antagonist pirenzepine, reduced the suppressant effect of the 5-HT1A receptor agonist 8-OH-DPAT on the spontaneous firing activity of rat dorsal raphe 5-HT neurons. Moreover, AF-64A-induced lesions of cholinergic neurons directly in the medial prefrontal cortex and after its i.c.v. injection attenuated the effect of 8-OH-DPAT. Finally, the NMDA receptor antagonist (+)MK-801 and the GABA(B) receptor antagonist SCH-50911, but not the GABA(A) receptor antagonist (-)bicuculline, dampened the latter response. The present study unveiled a key role for the cholinergic and GABAergic systems in the feedback inhibition of dorsal raphe 5-HT neurons.
Haddjeri
N
N
Department of Psychiatry, Brain Institute, University of Florida, Gainesville 32610-0256, USA.
Lucas
G
G
Blier
P
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D004594:Electrophysiology; D005246:Feedback; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin