Buspirone as an inhibitor of voluntary ethanol intake in male rats.
The effect of buspirone, a drug with mainly 5-HT1A-agonist activity, on voluntary ethanol intake was tested in a rat model of alcoholism. In this model the treatment consists of an injection of ethanol (2.0 g/kg) or saline once a week, preceded by a 24 h choice between water and ethanol (10% w/v). This weekly injection of ethanol reduces voluntary ethanol intake in male rats. Maximal inhibition is seen after 5-6 weeks. At this maximal inhibition buspirone or saline was injected prior to the voluntary 24 h intake of ethanol in both the ethanol- and saline-injected groups. The tested doses were 5 mg/kg (week 5) and 20 mg/kg (week 6). There was no reduction in ethanol intake in the buspirone-injected groups when compared with their corresponding controls. A second experiment with buspirone was performed during the evaluation period following treatment with ethanol. This treatment consisted of a choice between water and ethanol (10%, w/v) for 1 day each week, followed by an injection of ethanol 2.0 g/kg) and lasted for 52 weeks. During the evaluation period the rats had a continuous choice between ethanol and water for 37 weeks and no injections were given. In this situation, with a longer exposure to ethanol, a dose of 20 mg/kg of buspirone in week 90 reduced ethanol intake by approximately 40%, when compared with controls. The effect of this buspirone dose lasted at least a week. This indicates that the long-term exposure to ethanol in the second experiment induces changes that affect the serotonergic transmission, and that this changed neural system is involved in the regulation of voluntary ethanol intake.
Hedlund
L
L
Department of Pharmacology, University of Umeå, Sweden.
Wahlström
G
G
D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002065:Buspirone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D002065:Buspirone