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Psychopharmacology (Berl). 2009 Oct;206(3):447-56. doi: 10.1007/s00213-009-1622-4. Epub 2009 Aug 4.

Decreased reinforcing effects of cocaine following 2 weeks of continuous D-amphetamine treatment in rats.

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1
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Abstract

RATIONALE:

Recent studies have investigated D-amphetamine as a potential agonist medication for cocaine dependence. In rats, a 14-day continuous infusion of D: -amphetamine via osmotic mini-pump has been shown to decrease cocaine-reinforced responding under a progressive ratio (PR) schedule of reinforcement.

OBJECTIVES:

This study was designed to assess the influences of the D-amphetamine treatment dose and self-administered cocaine dose on the magnitude of this effect.

MATERIALS AND METHODS:

Experiment 1: rats were trained to self-administer 1.5 mg/kg/inj cocaine under a PR schedule, then implanted with D-amphetamine mini-pumps for 14 days (days 1-7, 5 mg/kg/day; days 8-14, 7.5 mg/kg/day). Breakpoints were evaluated throughout the treatment period and 14 days post-treatment. Experiment 2: rats were trained to self-administer cocaine under a PR schedule and initial dose-response curves were determined before implantation of D-amphetamine mini-pumps. During the 14-day D-amphetamine (5 mg/kg/day) treatment period, rats self-administered one of four cocaine doses (0.19, 0.38, 0.75, or 1.5 mg/kg/inj). A post-treatment PR dose-response curve and responding under a fixed ratio 1 (FR1) schedule were evaluated after mini-pump removal.

RESULTS:

Experiment 1: breakpoints for 1.5 mg/kg/inj cocaine were unchanged by the increasing dose of D-amphetamine. Experiment 2: the PR dose-response curve was shifted downward after the treatment period in rats that had self-administered 0.19 and 0.38 mg/kg/inj cocaine. In contrast, rats in the 0.75 and 1.5 mg/kg/inj groups demonstrated increased rates of cocaine intake under an FR1 schedule after the treatment period.

CONCLUSIONS:

These data suggest that continuous D-amphetamine treatment attenuates the reinforcing effects of cocaine.

PMID:
19652955
PMCID:
PMC2770337
DOI:
10.1007/s00213-009-1622-4
[Indexed for MEDLINE]
Free PMC Article
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