Effects of beta-carboline-3-carboxylic acid ethyl ester on suppressed and non-suppressed responding in the rhesus monkey.
The effects of the putative 'anxiogenic' compound beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) were studied on non-suppressed and suppressed responding of rhesus monkeys. Responding was maintained under a fixed-interval 2 min schedule of food presentation (non-suppressed responding) and a fixed-interval 2 min schedule of food presentation where each 10th response produced a 3-5 mA footshock (suppressed responding). Rates of suppressed responding were 60-90% lower than those for non-suppressed responding. beta-CCE reliably decreased non-suppressed responding over the range of 0.03-0.3 mg/kg (ED50 approximately 0.04 mg/kg) while consistent decreases in suppressed responding were not obtained in all animals until doses of 1-3 mg/kg (ED50 approximately 2 mg/kg) were given. Doses of beta-CCE greater than 0.01 mg/kg slightly increased blood pressure, moderately increased heart rate and greatly increased plasma ACTH levels for both types of response. In contrast, diazepam increased suppressed responding without affecting non-suppressed responding at low doses (0.3-1 mg/kg), while higher doses were required to decrease suppressed responding. Diazepam had little effect on blood pressure or mean heart rate. Ro 15-1788 (1 mg/kg) blocked the rate-decreasing effects of beta-CCE on non-suppressed responding, suggesting the decrease is mediated via a benzodiazepine recognition site. These results show that under conditions where relatively low doses of diazepam have an anxiolytic effect (i.e. selectively increase rates of suppressed responding), relatively low doses of beta-CCE selectively decrease non-suppressed responding, questioning current notions of how to define an anxiogenic drug effect.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D011678:Punishment; D012055:Reinforcement Schedule
D002243:Carbolines; D005442:Flumazenil; C024915:beta-carboline-3-carboxylic acid ethyl ester; D000324:Adrenocorticotropic Hormone; D003975:Diazepam