5-HT receptor ligands differentially affect operant oral self-administration of ethanol in the rat.
The present study evaluated the effects of the selective serotonin (5-hydroxyhyptamine; 5-HT) reuptake inhibitor, fluoxetine, the 5-HT1B receptor agonist, tetrahydro-4-pyridyl[3,2-b]pyridine, CP-94,253 the preferential 5-HT2A receptor agonist, 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane, DOI and the mixed 5-HT2C/1B receptor agonist, 1-(3-chlorophenyl)piperazine, mCPP, on oral ethanol (10% v/v) self-administration in a two-lever, fixed-ratio:1, water vs. ethanol choice procedure in the rat. All compounds affected operant behavior, with varying degrees of specificity, that is, the extent to which a reduction of ethanol-reinforced lever pressing coincided with a reduction of ethanol preference, and selectivity, that is, the extent to which a reduction of ethanol-reinforced lever pressing could be dissociated from an effect on total responding on both levers. Fluoxetine (5-20 mg/kg, i.p.) and CP-94,253 (1-10 mg/kg, i.p.) induced a nonselective disruption of operant behavior; the profile being weakly specific for CP-94,253. DOI (0.1-0.3 mg/kg, i.p.) and mCPP (0.3-1 mg/kg, i.p.) induced a specific effect; the profile being more selective for DOI. These findings suggest that operant ethanol self-administration can be suppressed in a specific manner by activation of 5-HT2A and, possibly, 5-HT2C receptors, and in a nonselective manner by activation of 5-HT1B receptors. As fluoxetine indirectly stimulates these receptors and its behavioral profile resembles more that of a 5-HT1B receptor agonist, activation of 5-HT1B receptors may underlie its effects on operant ethanol self-administration.
Maurel
S
S
CNS Research, Bayer, Wuppertal, Germany.
De Vry
J
J
Schreiber
R
R
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D005473:Fluoxetine / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012646:Self Administration; D012680:Sensitivity and Specificity; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000431:Ethanol; D005473:Fluoxetine; D008024:Ligands; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors