Neuropharmacological antagonism of the beta-carboline-induced "anxiety" response in rhesus monkeys.

A behavioral and physiological syndrome of stress-related responses was reported in primates following treatment with the benzodiazepine receptor antagonist, beta-carboline-3-carboxylic acid ethyl ester (beta-CCE). The behavioral and physiological effects of beta-CCE are similar to those observed during stressful or "anxiety"-related conditions characterized in rhesus monkeys under natural conditions. Pharmacological agents which are known to antagonize anxiety responses in other paradigms were tested for their ability to antagonize the actions of beta-CCE. Diazepam (1 mg/kg) completely blocked the effects of beta-CCE (200 micrograms/kg) on anxiety-related behaviors, heart rate and blood pressure, plasma catecholamines, cortisol, and adrenocorticotrophic hormone. A presynaptically active dose of the alpha-adrenoreceptor agonist, clonidine (10 micrograms/kg), significantly attenuated the effects of beta-CCE on all parameters, whereas the beta-adrenoreceptor agonist, propranolol (3 mg/kg), failed to alter the increases in plasma catecholamines, cortisol, or ACTH. In addition to these adrenergic agents, the serotonin antagonist, cyproheptadine (1 mg/kg), and the GABA-mimetic, 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyrindin-3-ol (1 mg/kg), partially blocked the behavioral, physiological, and biochemical changes after beta-CCE. Manifestation of the complete "anxiety" syndrome evoked by beta-CCE in primates may require the functional activity of several neurotransmitter systems.