Effects of chronic d-amphetamine treatment on cocaine- and food-maintained responding under a progressive-ratio schedule in rhesus monkeys.
BACKGROUND
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.
Negus
S Stevens
SS
Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. negus@mclean.harvard.edu
Mello
Nancy K
NK
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D004435:Eating / Q000187:drug effects; D005260:Female; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012646:Self Administration; D013997:Time Factors
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine