Alnespirone and buspirone have anxiolytic-like effects in a conflict procedure in rats by stimulating 5-HT(1A) receptors.

Abstract

We studied the anxiolytic-like activity of alnespirone and buspirone, two 5-HT(1A) receptor agonists, in a modified Geller-Seifter conflict model, and examined the role of 5-HT(1A) receptors by studying whether WAY-100635, a selective antagonist at these receptors, blocked their effects. Administered s.c. 30 minutes before testing, 0.5 and 1mg/kg alnespirone significantly increased punished responding, whereas lower doses (0.125 and 0.25 mg/kg) had no effect. At 1mg/kg, alnespirone significantly reduced the rates of unpunished responding. One dose of buspirone (1mg/kg) significantly increased punished responding and reduced unpunished responding. Lower doses were ineffective. Administered s.c. 40 minutes before testing, WAY-100635 had no effect on any parameter but completely antagonized the effects of alnespirone (1mg/kg) and buspirone (1mg/kg) on punished responding. The ability of buspirone to reduce unpunished responding was not antagonized by WAY-100635, probably reflecting a sedative effect of buspirone due to dopamine D2 receptor blockade. The results suggest that alnespirone and buspirone have anxiolytic-like activity in a conflict procedure by stimulating 5-HT(1A) receptors, presumably at a presynaptic level. Like buspirone, alnespirone may have useful effects in the treatment of anxiety disorders.

• Authors: L Cervo, C Munoz, A Bertaglia, R Samanin
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 11 Issue 2 Pg. 153-60 (Apr 2000) ISSN: 0955-8810 [Print] England
• PMID: 10877120 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Piperazines
• Pyridines
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT1
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Spiro Compounds
• alnespirone
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• Buspirone

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Buspirone (pharmacology)
• Conditioning, Operant (drug effects)
• Conflict, Psychological
• Male
• Piperazines (pharmacology)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (drug effects)
• Receptors, Serotonin, 5-HT1
• Reinforcement Schedule
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Spiro Compounds (pharmacology)