Using a rich-lean transition procedure to evaluate putative antianxiety medications.

Area of Science:

• Behavioral Neuroscience
• Pharmacology
• Psychopharmacology

Background:

• Traditional antianxiety medication assessment relies on aversive stimuli like shock, posing practical challenges in nonhuman primates.
• Rich-lean transitions in reinforcement schedules disrupt operant behavior, a disruption that benzodiazepines can ameliorate, suggesting a potential alternative assessment method.

Purpose of the Study:

• To evaluate the feasibility and utility of a rich-lean transition procedure for the preclinical assessment of potential antianxiety medications without employing shock.
• To determine if this procedure can differentiate between anxiolytic and anxiogenic drug effects.

Main Methods:

• Adult rhesus monkeys' lever-pressing behavior was reinforced under a two-component multiple schedule with rich (4 pellets) and lean (1 pellet) components.
• Sessions included irregular transitions between components (lean-lean, lean-rich, rich-lean, rich-rich) to observe behavioral disruptions, specifically pausing after rich-lean transitions.
• The effects of benzodiazepines (midazolam, alprazolam), an imidazotriazine (TPA-023B), morphine, and (+)amphetamine on rich-lean pausing were assessed.

Main Results:

• Rich-lean transitions reliably induced extended pausing behavior in rhesus monkeys.
• Benzodiazepines and TPA-023B selectively reduced this pausing, consistent with anxiolytic effects.
• Morphine and (+)amphetamine selectively increased pausing, indicating anxiogenic-like effects.

Conclusions:

• The rich-lean transition procedure is a viable and effective method for preclinical evaluation of antianxiety medications in nonhuman primates.
• This shock-free paradigm demonstrates utility in identifying potential anxiolytic and anxiogenic compounds based on their modulation of behavioral disruption.