213 112 112 1 1 Rudy Schreiber Klaus Opitz Thomas Glaser Jean De Vry Department of Psychopharmacology, Troponwerke Institute for Neurobiology Berliner Strasse 156 5000 Cologne 80 Germany Institute for Pharmacology and Toxicology, University of Muenster Domagkstrasse 12 Muenster Germany Abstract The selective serotonin(5-HT) 1A receptor agonists 8-OH-DPAT and ipsapirone were tested in selectively inbred Wistar rats, with high preference (70–90%: defined as the ratio of ethanol (EtOH) to total fluid intake) for EtOH (10% v/v) over water in a two-bottle free choice situation. Rats were injected shortly before the overnight test session (8:00 p.m. –8:00 a.m. ). EtOH and water consumption were determined in 20-min intervals; food consumption after the session. 8-OH-DPAT (ED 50 : 2.4 mg/kg, SC) and ipsapirone (ED 50 : 12.5 mg/kg, SC) reduced EtOH preference in a dose-dependent manner. In addition, 8-OH-DPAT increased total fluid intake, whereas ipsapirone enhanced total food intake. The EtOH preference reduction was time-dependent and reached a maximum within the second 4 h after application of 8-OH-DPAT (−73%) and ipsapirone (−72%). The preference reducing effect of ipsapirone (20 mg/kg, PO) was completely blocked by the nonselective 5-HT 1A antagonist spiperone (0.05 mg/kg, SC). Local application of 8-OH-DPAT (10 µg, 0.5 µl) into the dorsal raphe nucleus (DRN, a brain area rich in somatodendritic 5-HT 1A autoreceptors), reduced the EtOH preference significantly as compared to the saline injection in the same animal (−12%, 8:00–12:00 p.m. ). Only marginal effects on ingestion behavior were observed after micro-injection into the nucleus accumbens. Reduction of brain 5-HT levels by pretreatment with the 5-HT synthesis inhibitor pCPA (2×150 mg/kg, IP) resulted in a short lasting, marked reduction (−54%) and a long lasting, small attenuation of the EtOH preference. Total food consumption was strongly decreased but returned soon to normal; total fluid intake was only slightly decreased. The EtOH preference reducing effect of ipsapirone (5 and 20 mg/kg, SC) was attenuated in pCPA-pretreated rats. The present data suggest that 5-HT 1A receptor ligands reduce EtOH preference via stimulation of 5-HT 1A receptors in the DRN. The possibility of additional mechanism(s) is discussed.
Psychopharmacology – Springer Journals
Published: Aug 1, 1993
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