A primate model of anxiety

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Pentylenetetrazol (PTZ) is a chemical convulsant used to induce seizure activity.
• Anxiogenic effects of PTZ in non-human primates are not well-characterized.
• Rhesus monkeys offer a relevant model for studying anxiety due to their complex social behavior.

Purpose of the Study:

• To investigate the anxiogenic effects of Pentylenetetrazol (PTZ) in rhesus monkeys.
• To evaluate the efficacy of various pharmacological agents in antagonizing PTZ-induced behavioral and physiological changes.
• To establish PTZ as a potential model for assessing anxiolytic drug activity.

Main Methods:

• Administration of Pentylenetetrazol (PTZ) at 30 mg/kg, i.m. to acclimatized rhesus monkeys.
• Observation of behavioral changes including hypervigilance, aggressiveness, and altered posture.
• Measurement of plasma cortisol levels as a physiological stress marker.
• Administration of benzodiazepines (diazepam, alprazolam), buspirone, promethazine, and sodium valproate to assess their effects on PTZ-induced responses.

Main Results:

• PTZ induced significant anxiogenic behaviors and elevated plasma cortisol levels in rhesus monkeys.
• Benzodiazepines (diazepam, alprazolam) effectively antagonized both behavioral and cortisol changes induced by PTZ.
• Buspirone blocked behavioral effects but did not attenuate the rise in plasma cortisol.
• Promethazine and sodium valproate did not mitigate the effects of PTZ, indicating response specificity.

Conclusions:

• Pentylenetetrazol (PTZ) reliably induces an anxiogenic state in rhesus monkeys.
• The PTZ model in rhesus monkeys is sensitive to benzodiazepine intervention.
• This model shows promise for the preclinical evaluation of novel anxiolytic agents.