The novel 5-HT2 receptor antagonist, RP 62203, selectively blocks serotoninergic but not dopaminergic-induced inhibition in the rat prefrontal cortex.
The influence of the novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, RP 62203, on serotoninergic neurotransmission was investigated using an in vivo electrophysiological technique. For this purpose, the ability of RP 62203 (1-3 mg/kg i.p.) to block the inhibitory responses of prefrontal cortical neurons induced by electrical stimulation of the median raphe nucleus was examined in anesthetized rats. In addition, the effects of RP 62203 on the dopaminergic inhibitory responses induced in the prefrontal cortex by stimulation of the ventral tegmental area and on the enhancement of these responses by lysergic acid diethylamide (LSD, a 5-HT2 receptor agonist, 30 or 60 micrograms/kg i.p.), were analyzed. RP 62203 blocked the inhibition induced by median raphe nucleus stimulation in a dose-dependent and reversible fashion. In contrast, RP 62203 failed to affect the inhibitory responses induced in prefrontal cortical cells by stimulation of the ventral tegmental area. However, the enhancement by LSD of the inhibition induced by stimulation of the ventral tegmental area in the prefrontal cortex was blocked by RP 62203. These results demonstrate that RP 62203 selectively blocks serotoninergic, but not dopaminergic, neurotransmission in the prefrontal cortex.
Godbout
R
R
Chaire de Neuropharmacologie, INSERM U 114, Collège de France, Paris.
Mantz
J
J
Glowinski
J
J
Thierry
A M
AM
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003499:Cyclic S-Oxides / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D003499:Cyclic S-Oxides; D009281:Naphthalenes; D012702:Serotonin Antagonists; D012701:Serotonin; C070475:fananserin; D008238:Lysergic Acid Diethylamide; D004298:Dopamine