Interactive effects of cholecystokinin-8S and serotonin on spontaneously active neurons in ventromedial hypothalamic slices.
The influence of cholecystokinin (CCK-8S) and serotonin (5-HT) on the discharge rate of spontaneously active ventromedial hypothalamic (VMH) neurons was investigated in brain slices. Drugs were drop-applied individually and concomitantly into the slice chamber. CCK-8S (0.1-2.5 microM) produced a dose-dependent increase in firing rate mainly mediated by the CCK(B) receptor subtype, because Suc-CCK-4 (a CCK(B) receptor agonist) acted like CCK-8S and A-71378 (a CCK(A) receptor agonist) rarely induced excitatory effects. The main response to serotonin application (2-20 microM) was an inhibition that could be mimicked by 8-OH-DPAT (a 5-HT1A receptor agonist). S-UH-301 (a 5-HT1A receptor antagonist) reversibly diminished or blocked this effect. Other 5-HT agonists like DOI and 2-Methyl-5-HT did not evoke relevant responses. Co-administration of CCK-8S and 5-HT induced counteracting effects at which CCK-8S significantly reduced the prevailing suppressive effect of serotonin. It is concluded that both substances, CCK and 5-HT, have a reciprocal influence on the regulation of neuronal activity within the VMH, a structure, which is involved in the mediation of signals for the state of satiety.
Heidel
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Institute of Physiology, Department of Neurophysiology, Charité, Humboldt-University, Berlin, Germany. heidel@rz.charite.hu-berlin.de
Davidowa
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
C090019:8-sulfocholecystokinin octapeptide; D000662:Amphetamines; D009842:Oligopeptides; D011949:Receptors, Cholecystokinin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C063897:A 71378; D012701:Serotonin; C045918:2-methyl-5-HT; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012844:Sincalide; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine