Effects of ketanserin on neuronal responses to serotonin in the prefrontal cortex, lateral geniculate and dorsal raphe nucleus.
The ability of the putative serotonin2 (5-HT2) antagonist ketanserin, to alter serotonin (5-HT)-induced responses in cell firing was examined in the prefrontal cortex, the lateral geniculate nucleus and the dorsal raphe nucleus of the rat by microiontophoretic extracellular single unit recording techniques. In the prefrontal cortex, ketanserin failed to antagonize the inhibitory effects of 5-HT recorded in cerveau isolé or preparations anesthetized with chloral hydrate (pure excitatory responses to 5-HT were not observed in either of these preparations). Paradoxically, the inhibitory response produced by 5-HT (but not gamma-aminobutyric acid, tryptamine or norepinephrine) was potentiated, even in cells where ketanserin alone did not alter spontaneous firing rates. The systemic administration of ketanserin (5 mg/kg, i.p.) had effects similar to those observed in the microiontophoretic experiments in the prefrontal cortex. In the dorsal raphe nucleus of animals anesthetized with chloral hydrate, ketanserin neither attenuated nor potentiated the inhibition of serotonergic neurons by 5-HT. In the lateral geniculate nucleus, as in the prefrontal cortex, ketanserin potentiated rather than attenuated, the inhibitory effect of 5-HT. Ketanserin was found to attenuate the excitatory responses produced by norepinephrine, an alpha 1-adrenoceptor-mediated response, in the lateral geniculate nucleus. The observed potentiation by ketanserin of inhibitory responses to 5-HT but not those of gamma-aminobutyric acid, tryptamine or norepinephrine, recorded in the prefrontal cortex, may be consistent with the proposed interaction between ketanserin and a specific 5-HT2 binding site.(ABSTRACT TRUNCATED AT 250 WORDS)
Lakoski
J M
JM
Aghajanian
G K
GK
D000818:Animals; D003655:Decerebrate State / Q000503:physiopathology; D004594:Electrophysiology; D005625:Frontal Lobe / Q000187:drug effects*; D005829:Geniculate Bodies / Q000187:drug effects*; D007650:Ketanserin; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D010880:Piperidines; D014363:Tryptamines; D012701:Serotonin; C030820:tryptamine; D005680:gamma-Aminobutyric Acid; D007650:Ketanserin; D009638:Norepinephrine