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

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.

• Authors: Keri A Chiodo, David C S Roberts
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 206 Issue 3 Pg. 447-56 (Oct 2009) ISSN: 1432-2072 [Electronic] Germany
• PMID: 19652955 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Central Nervous System Stimulants
• Cocaine
• Dextroamphetamine

Topics

• Animals
• Behavior, Animal (drug effects)
• Central Nervous System Stimulants (administration & dosage, pharmacology)
• Cocaine (administration & dosage, pharmacology)
• Cocaine-Related Disorders (drug therapy)
• Dextroamphetamine (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Male
• Rats
• Rats, Sprague-Dawley
• Reinforcement Schedule
• Self Administration