Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus.
Slices of rat hypothalamus prelabeled with [3H]-5-hydroxytryptamine ([3H]-5-HT) were superfused and the release of the labeled transmitter was elicited either by electrical stimulation or by fenfluramine. Whereas the electrically stimulated release of [3H]-5-HT was completely abolished by removing calcium from the superfusion medium, the fenfluramine-induced release of [3H]-5-HT was calcium-independent. Methiothepin increased, in a concentration-dependent manner, the [3H]-5-HT release induced by electrical stimulation but had no effect on that elicited by fenfluramine. The 3H-transmitter release elicited by electrical stimulation was inhibited by lysergic acid diethylamide (LSD) in a concentration-dependent manner, but the release induced by fenfluramine was not modified by LSD. The reduction by LSD of [3H]-5-HT overflow elicited by electrical stimulation was antagonized by methiothepin, but unaffected by phentolamine or by sulpiride. Low concentrations (10-1000 nM) of citalopram, a 5-HT uptake inhibitor, antagonized the inhibition by LSD of electrically evoked release of [3H]-5-HT. These concentrations of citalopram did not modify by themselves the overflow of [3H]-5-HT elicited by electrical stimulation. It is concluded that the modulation of [3H]-5-HT release by presynaptic serotonin autoreceptors is not operational when the neurotransmitter is released through a calcium-independent mechanism. The potent presynaptic inhibition by LSD of serotonergic neurotransmission may contribute to the central actions of this drug. The interaction between citalopram and LSD at the level of [3H]-5-HT release does not seem to involve a competitive interaction at the same receptor site. The possibility that neuronal uptake of 5-HT and the presynaptic 5-HT autoreceptor may be linked in a functional manner cannot be excluded.
D000818:Animals; D002118:Calcium / Q000502:physiology; D015283:Citalopram; D004558:Electric Stimulation; D005277:Fenfluramine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects*; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000037:antagonists & inhibitors*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011437:Propylamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D005277:Fenfluramine; D008719:Methiothepin; D008238:Lysergic Acid Diethylamide; D002118:Calcium