Effects of 5,7-dihydroxytryptamine lesion of the dorsal raphe nucleus on ethanol discrimination in the rat.
It has been shown that ethanol produces a complex interoceptive cue in rodents with distinct GABAergic, glutamatergic, and serotonergic (5-hydroxytryptamine, 5-HT) components. The present study aimed to examine the contribution of the 5-HT system originating in the dorsal raphe nucleus (DRN) to the discriminative stimulus effects of ethanol in male Wistar rats. Therefore, selective lesions of 5-HT neurons in the DRN were induced by microinfusions of 5,7-dihydroxytryptamine. The DRN- and sham-lesioned rats were trained to discriminate ethanol (1.0 g/kg) from saline in a standard two-lever drug discrimination procedure. Acquisition of ethanol discrimination and discrimination performance after consumption of lower doses of ethanol did not differ between the groups. In substitution tests, diazepam (0.5-2.5 mg/kg), a nonselective benzodiazepine receptor agonist, partially generalized from the ethanol cue in both groups. In contrast, m-chlorophenylpiperazine (0.1-0.9 mg/kg), a mixed 5-HT(1B/2C) receptor agonist, did not mimic the ethanol cue. The drug decreased response rates in both groups, but this effect was more evident in the sham-lesioned group. A 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propyloamino)-tetraline (0.05-0.4 mg/kg), did not produce significant increase in ethanol-appropriate responding in either group. These results may indicate that 5-HT neurons of the DRN are not critically involved in ethanol discrimination in the rat.
Koros
Eliza
E
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, 9 Sobieskiego St., PL-02957 Warsaw, Poland.
Bienkowski
Przemyslaw
P
Kostowski
Wojciech
W
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects; D018490:Serotonin Agents / Q000633:toxicity*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D018490:Serotonin Agents; D013764:Tetrahydronaphthalenes; D044282:Receptor, Serotonin, 5-HT1A; D015116:5,7-Dihydroxytryptamine; D000431:Ethanol; D003975:Diazepam; C015068:1-(3-chlorophenyl)piperazine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin