Effects of β-carboline-3-carboxylic acid ethyl ester on suppressed and non-suppressed responding in the rhesus monkey

The effects of the putative 'anxiogenic' compound β-carboline-3-carboxylic acid ethyl ester (β-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. β-CCE reliably decreased non-suppressed responding over the range of 0.03-0.3 mg/kg (ED₅₀ ∼ 0.04 mg/kg) while consistent decrease in suppressed reponding were not obtained in all animals until doses of 1-3 mg/kg (ED₅₀ ∼ 2 mg/kg) were given. Doses of β-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 β-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 β-CCE selectively decrease non-suppressed responding, questioning current notions of how to define an anxiogenic drug effect.