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.
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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)
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Chemical References |
- Central Nervous System Stimulants
- Cocaine
- Dextroamphetamine
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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
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