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Effects of chronic d-amphetamine treatment on cocaine- and food-maintained responding under a progressive-ratio schedule in rhesus monkeys

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Abstract

Rationale

d-Amphetamine is a candidate agonist medication for the treatment of cocaine dependence, and evaluation of d-amphetamine effects on abuse-related effects of cocaine in preclinical assays is warranted.

Objective

This study was designed to assess the effects of chronic d-amphetamine treatment on cocaine- and food-maintained responding under a progressive-ratio schedule in rhesus monkeys. The effects of schedule manipulations on cocaine and food-maintained responding were also examined for comparison with d-amphetamine effects.

Methods

Key-press responding under a progressive-ratio schedule resulted in the delivery of cocaine (0.032 mg/kg per injection) or 1 g food pellets. The effect of manipulating cocaine dose (saline, 0.001–0.1 mg/kg per injection) or the number of food pellets delivered (0, 1 and 4 pellets) was determined. Subsequently, three schedule parameters were manipulated: (1) starting ratio value, (2) increments of the ratio progression, and (3) duration of post-reinforcer time-outs when the ratio value was constant. Finally, the effects of 10-day treatment with d-amphetamine (0.01–0.1 mg/kg per hour) were examined.

Results

Break points increased as a function of cocaine dose or the number of food pellets, and similar break points were maintained by delivery of 0.032 mg/kg per injection cocaine and 1 food pellet. Manipulation of schedule parameters produced similar effects on responding maintained by cocaine (0.032 mg/kg per injection) or food (1 pellet). In contrast, d-amphetamine produced a dose-dependent decrease in cocaine-maintained responding and had less consistent effects on food-maintained responding.

Conclusions

These results are consistent with the hypothesis that chronic treatment with d-amphetamine decreases cocaine self-administration in rhesus monkeys, possibly by attenuating the reinforcing effects of cocaine.

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Acknowledgements

This research was supported in part by grants P01-DA14528 and KO5-DA00101 from the National Institute on Drug Abuse, NIH.

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Authors and Affiliations

  1. Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA

    S. Stevens Negus & Nancy K. Mello

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  1. S. Stevens Negus
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  2. Nancy K. Mello
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Correspondence to S. Stevens Negus.

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Negus, S.S., Mello, N.K. Effects of chronic d-amphetamine treatment on cocaine- and food-maintained responding under a progressive-ratio schedule in rhesus monkeys. Psychopharmacology 167, 324–332 (2003). https://doi.org/10.1007/s00213-003-1409-y

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  • DOI: https://doi.org/10.1007/s00213-003-1409-y

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