Effects of buspirone and related compounds on suppressed operant responding in rats.
The novel anxiolytic drug buspirone and its analogues, gepirone and ipsapirone, have behavioral effects that differ substantially from those of other anxiolytics such as benzodiazepines and barbiturates. In particular, buspirone does not consistently produce large increases in rates of responding suppressed by punishment in rodents or primates. To study the effects of buspirone and other compounds on suppressed operant responding in rats, two procedures were used. In the first, food-reinforced responding was suppressed during a stimulus associated with response-produced electric shocks (punishment). Chlordiazepoxide produced large increases in rates of punished responding, but neither buspirone nor ipsapirone gave rise to a similar effect. In a second experiment, food-reinforced responding was suppressed during a stimulus that terminated with an unavoidable shock (conditioned emotional response). Chlorodiazepoxide and clorazepate increased suppressed response rates at low doses and decreased nonsuppressed responding at higher doses, giving rise to dose-related increases in suppression ratios. The effects of buspirone, gepirone and ipsapirone were similar to those of the benzodiazepines with ipsapirone producing particularly marked increases in responding during the pre-shock stimulus. 8-Hydroxy-2-(di-n-propylamino)tetralin did not consistently give rise to the same effect. In addition, similar effects were not produced by haloperidol, imipramine, morphine or idazoxan. Haloperidol and morphine decreased nonsuppressed responding without changing rates of suppressed responding or suppression ratios. Imipramine decreased rates of both nonsuppressed and suppressed responding and idazoxan decreased suppression ratios. The conditioned emotional response procedure may be more sensitive for assessing the behavioral effects of buspirone and similar anxiolytic drugs in rats than are punishment procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
Sanger
D J
DJ
Synthelabo Recherche (L.E.R.S), Bagneux, France.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D007274:Injections, Intraperitoneal; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; D004146:Dioxanes; D011743:Pyrimidines; C043077:ipsapirone; D002707:Chlordiazepoxide; C039979:gepirone; D002065:Buspirone; D019329:Idazoxan