Title

Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats

Document Type

Article

Publication Date

1-1-1984

Abstract

In the presence of a stimulus above the center lever, monkeys and rats were required to complete one of two fixed-ratios (FRs) on the center lever (FR20 or FR40, monkeys; FR8 or FR16, rats). Completion on the ratio turned off the center-lever stimulus and produced a stimulus above each of the two side levers. If the completed ratio was high (e.g. FR40), a response on the left lever produced a food pellet. If the ratio was low (e.g., FR20) a response on the right lever produced food. Errors produced a brief timeout. In monkeys, d-SKF 10,047 either increased slighly or had no effect on response rate on the center lever, whereas increasing errors in a dose-related manner. In rats, both dl-SKF 10,047 and cyclazocine were found to produce a dose-related decrease in response rate and an increase in errors. The putative kappa agonist ethylketocyclazocine produced similar effects in both the monkey and rat. At doses that dcreased rate of responding, accuracy was unaffected, except at the highest dose that virtually eliminated responding. Unlike any of the other drugs tested, ethylketocyclazocine decreased rate by producing a dose-related pause at the start of the session rather than by altering the local rates of responding. In monkeys, the mu agonists morphine and methadone produced dose-related decreases in response rate, primarily due to sporadic pausing. Across this same range of doses neither drug affected errors, except at the high doses in which relatively small increases obtained. In contrast, in the rat, morphine produced a dose-related decrease in response rate and an increase in errors. At several lower doses errors were increased whereas response rate was unaffected. The effects of buprenorphine also differed between the species. In the monkey, doses as high as 3.2 mg/kg had no effect on the discriminative performances. Whereas in the rat, buprenorphine decreased rate and increased errors in a manner similar to that of morphine. The data suggest that the putative mu, kappa and sigma agonists studied exert greater differential effects on the accuracy of a discrimination in monkeys than in rats. The results are consistent with the notion that, in monkeys, opioids with activity at the putative sigma receptor exert disruptive effects on the accuracy of discriminations, an action not shared by prototypical mu and kappa agonists, at doses that produce comparable rate-decreasing effects.

Publication Source (Journal or Book title)

Journal of Pharmacology and Experimental Therapeutics

First Page

541

Last Page

549

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