Possible mechanism of action for the attenuation of ethanol intake induced by ritanserin in rats.
The 5-HT2 receptor antagonist, ritanserin, reduces alcohol intake in rats and the nucleus accumbens (NAC) has been proposed as a site of action for the drug. Recent microdialysis studies have shown that acute subcutaneous (SC) administration of ritanserin increases extracellular 5-HT levels in the NAC. The present study evaluated, in genetically heterogeneous rats with developed preference for 3% ethanol, whether the attenuation of ethanol intake induced by ritanserin might be related to its effect on the synaptic availability of 5-HT in the NAC. Damaging 5-HTergic neurons by intracerebroventricular infusion of 5,7-dihydroxytryptamine (5,7-DHT) abolished the effect of ritanserin on ethanol consumption. Injections of the 5-HT3 receptor antagonist MDL 72222 into the NAC significantly reduced the inhibitory effect of SC injection of ritanserin, 1 mg/kg, and completely abolished the effect of ritanserin, 0.1 mg/kg. Subcutaneous injections of MDL 72222, 0.3 mg/kg 3 times/day, suppressed the effect of SC ritanserin, 0.1 mg/kg. The present findings, together with those of previous experiments showing that the tryptophan hydroxylase inhibitor p-chlorophenylalanine abolishes the effect of ritanserin, support the hypothesis that its effect on ethanol intake may be due to increased synaptic availability of 5-HT into the NAC.
Panocka
I
I
Institute of Pharmacology, University of Camerino, Italy.
Ciccocioppo
R
R
Polidori
C
C
Romagnoli
S
S
Froldi
R
R
Massi
M
M
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000428:Alcohol Drinking / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000097:blood; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016713:Ritanserin / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D014326:Tropanes / Q000494:pharmacology
D015116:5,7-Dihydroxytryptamine; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D016713:Ritanserin; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014326:Tropanes; C042253:bemesetron