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


OBJECTIVE
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.


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.
Chiodo
Keri A
KA
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Roberts
David C S
DC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration
D000697:Central Nervous System Stimulants; D003042:Cocaine; D003913:Dextroamphetamine