Effects of triazolam, 8-OH-DPAT, and buspirone on repeated acquisition in squirrel monkeys.

Abstract

The nonserotonergic benzodiazepine, triazolam, was compared with two 5-HT1A receptor agonists, 8-OH-DPAT and buspirone, in squirrel monkeys responding under a repeated-acquisition procedure. In each session, subjects acquired a 4-response sequence by responding sequentially on 3 keys in the presence of 4 discriminative stimuli (colors). Response sequences for each session were maintained by food presentation under a second-order fixed-ratio schedule. Errors produced a brief time-out but did not reset the sequence. In general, all of the drugs produced dose-dependent decreases in overall response rate and increases in the percentage of errors as the cumulative dose was increased. Together, these results indicate that 5-HT1A receptor agonists disrupt learning in squirrel monkeys by producing rate-decreasing and error-increasing effects in a manner comparable with the nonserotonergic benzodiazepine triazolam.

EFFECTS OF GABAA MODULATORS ON THE REPEATED ACQUISITION OF RESPONSE SEQUENCES IN SQUIRREL MONKEYS

“…When subjects responded under either a chain-strained or tandem-strained condition, triazolam was found to produce rate-decreasing and small error-increasing effects. The disruptive effects of triazolam were comparable to those reported previously in squirrel monkeys (Winsauer et al, 2002), patas monkeys (Brocklehurst, Devia, Faust, & Moerschbaecher, 1987), and humans (Bickel et al, 1990) responding under similar repeated-acquisition procedures. For example, in patas monkeys responding under a multiple schedule of acquisition and performance of con-ditional discriminations, triazolam produced dose-related decreases in response rates in both components of the multiple schedule.…”

“…The volume of both drug and vehicle (control) injections was 0.5 ml/kg of body weight and these injections were administered in the gluteus muscle before the start of the experimental session. The dose range for each drug was determined from published literature (e.g., Auta, Winsauer, Faust, Lambert, & Moerschbaecher, 1997;Winsauer, Delatte, Stevenson, & Moerschbaecher, 2002) or by preliminar y determinations (not shown), and the time of injection was selected to ensure the onset of the effects of each drug prior to the beginning of the session. The time of injection prior to the session was 20 min for ␤-CCE, ␤-CCM and FG -7142, 5 min for flumazenil, and 30 min for triazolam.…”

Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus.

“…An example of a typical set of six sequences was as follows: LRCRC, CLRLR, LRLCL, RCRLC, CLCRL, RCLCR, with the order of the geometric symbols always squares, horizontal bars, triangles, vertical bars, and circles. The sequences were carefully selected to be equivalent in several ways and there were restrictions on their ordering across sessions (for restrictions, see Winsauer, Moerschbaecher, et al, 2002). …”

“…Identifying preclinical research techniques that can also be used with humans is a significant challenge, particularly for relatively complex cognitive abilities that require learning or memory, because few techniques are capable of repeatedly assaying the effects of a neurotoxic insult over time (see Winsauer & Mele, 1993). The repeated-acquisition task is particularly well suited for studying the effects of drugs on learning because it is (a) valid and generalizable in humans, nonhuman primates, and rodents (Bickel, Hughes, & Higgins, 1989; Brodkin & Moerschbaecher, 1997; Kamien, Bickel, Higgins, & Hughes, 1994; Nakamura-Palacios, Winsauer, & Moerschbaecher, 2000; Winsauer, Lambert, & Moerschbaecher, 1999), (b) able to assess both the quantity and quality of behavior (Cohn, Ziriax, Cox, & Cory-Slechta, 1992), (c) sensitive to numerous drugs and drug classes (e.g., Thompson, Winsauer, & Mastropaolo, 1987; Winsauer, Delatte, Stevenson, & Moerschbaecher, 2002), (d) capable of detecting the chronic effects of a drug (Cohn, Cox, & Cory-Slechta, 1993; Delatte, Winsauer, & Moerschbaecher, 2002; Thompson, 1974), and (e) useful for assessing the effects of pharmacological challenges in animals with neurotoxic lesions (Cohn & Cory-Slechta, 1993). …”