A re-evaluation of the role of alpha 2-adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat.
1. The acute behavioural effects of the alpha2-adrenoceptor antagonists, yohimbine, idazoxan and delequamine (RS-15385-197) were compared in two tests of exploratory behaviour in the rat, operated in tandem. These were the elevated X-maze test (5 min) and a modified holeboard test (12 min), which comprised a holeboard arena with a small roof in one corner as a 'refuge'. Rats were first placed into this corner, thus enabling measurements of initial emergence latency and the number of forays. The experiments were always done with a concomitant vehicle control group, with 10-12 rats per group, and with the treatment blinded. 2. In order to validate the tests, the effects of representatives of four classes of psychoactive agents were examined, viz. picrotoxin (anxiogenic), chlordiazepoxide (anxiolytic), (+)-amphetamine (stimulant) and diphenhydramine (sedative). The modified holeboard tended to be more sensitive than the measurement of total arm entries in the elevated X-maze at detecting drug effects on exploratory behaviour, but unlike the X-maze it could not clearly identify each class of agent. Thus, picrotoxin (5 mg kg(-1), i.p.) reduced total arm entries and open arm exploration in the X-maze (P<0.02) and suppressed most measures of activity in the holeboard (P<0.05); chlordiazepoxide (7.5 mg kg(-1), i.p.) increased total arm entries and open arm exploration (P<0.02) in the X-maze, without clear-cut effects in the holeboard; (+)-amphetamine (1 mg kg(-1), i.p.) had no significant effects in the X-maze, but increased most holeboard activities (P<0.05), and diphenhydramine (30 mg kg(-1), i.p.) reduced total arm entries in the X-maze (P<0.002) and hole exploration in the holeboard (P<0.05).
Redfern
W S
WS
Department of Pharmacology, Syntex Research Centre (now Quintiles Scotland Ltd), Heriot-Watt University Research Park, Riccarton, Edinburgh.
Williams
A
A
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015878:Mydriasis / Q000139:chemically induced; D009287:Naphthyridines / Q000008:administration & dosage / Q000494:pharmacology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000661:Amphetamine; D000697:Central Nervous System Stimulants; D002707:Chlordiazepoxide; D003000:Clonidine; D004146:Dioxanes; D004155:Diphenhydramine; D006993:Hypnotics and Sedatives; D019329:Idazoxan; D007093:Imidazoles; D007546:Isoquinolines; D009287:Naphthyridines; D010852:Picrotoxin; D015016:Yohimbine; C060956:Delequamine