Comparison of the effects of typical and atypical anxiolytics on learning in monkeys and rats.

Atypical anxiolytics such buspirone have been reported to produce fewer disruptive effects on complex behaviors than some typical anxiolytics from the benzodiazepine class. To extend this analysis, several drugs from both drug classes were directly compared in two species (rhesus monkeys and rats) using a repeated-acquisition procedure. In monkeys responding under a multiple schedule of reinforcement consisting of acquisition (learning) and performance components, buspirone (0.032-0.52 mg/kg), 8-hydroxy-dipropylaminotetralin (8-OH-DPAT;0.032-0-56 mg/kg), chlordiazepoxide (CDZP; 1-56 mg/kg) and alprazolam (0.032-0.32 mg/kg) produced dose-dependent decreases in overall response rate in all subjects. However, with buspirone and 8-OH-DPAT, these rate-decreasing effects occurred in acquisition at lower doses than in performance. The effects on overall accuracy (i.e., percent errors) in monkeys were variable across drugs and drug classes. Both 8-OH-DPAT and alprazolam produced large increases in percent errors in acquisition at doses that had little or no effect on errors in performance. Buspirone also had differential effects on percent errors across components, but the error-increasing effects in acquisition were smaller. CDZP administered either orally or intramuscularly produced only small increases in errors, and these occurred at doses that substantially decreased the overall rate of responding in both components of the multiple schedule. In rats responding under a repeated-acquisition procedure, buspirone (1-5.6 mg/kg), 8-OH-DPAT (0.056-3.2 mg/kg) and CDZP (1.8-32 mg/kg) produced dose-dependent decreases in overall response rate. Similar to acquisition data in monkeys, buspirone and 8-OH-DPAT also increased percent errors to a greater extent than CDZP. These data indicate that learning is sensitive to disruption by drugs with 5-HT1A agonist properties, and that atypical anxiolytics with 5-HT1A agonist properties are no less disruptive to "cognitive" processes than typical anxiolytics such as the benzodiazepine alprazolam.