Effects of dopamine receptor antagonists (D1 and D2) on the demand for smoked cocaine base in rhesus monkeys.
BACKGROUND
Previous studies suggest that dopamine antagonists may reduce the reinforcing effects of cocaine. However, the effects of these antagonists on the demand for smoked cocaine base have not been quantified.


OBJECTIVE
To evaluate the effects of selective D1 (SCH 23390) and D2 (raclopride) dopamine receptor antagonists on the demand for smoked cocaine base in rhesus monkeys using a behavioral economic analysis.


METHODS
Six rhesus monkeys were trained to self-administer smoked cocaine base (1.0 mg/kg/delivery) under chained fixed-ratio (FR) schedules (FR64, 128, 256, 512, 1024 or 2048 for lever presses and FR5 for inhalations) during daily 4-h sessions. A maximum of ten smoke deliveries were available. After 5 days of stable behavior at each FR, SCH 23390 (0.01 and 0.056 mg/kg) or raclopride (0.03 and 0.056 mg/kg) were injected intramuscularly, before each session, for 3 consecutive days.


RESULTS
Pretreatment with both antagonists dose-dependently reduced cocaine intake across most FR values tested; however, the decrease in consumption was greater at the higher unit prices than at the lower unit prices. A statistical estimate of the price (FR) at which maximum responding occurred (Pmax) was decreased during drug pretreatment, indicating weakened reinforcing effectiveness of cocaine.


CONCLUSIONS
These data suggest that both antagonists reduce the reinforcing effectiveness of smoked cocaine base, and they have a greater effect on cocaine consumption at higher FR values.
Campbell
U C
UC
Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455-0392, USA. savag009@gold.tc.umn.edu
Rodefer
J S
JS
Carroll
M E
ME
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D016578:Crack Cocaine / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012054:Reinforcement, Psychology; D012457:Salicylamides / Q000494:pharmacology*; D012646:Self Administration
D001552:Benzazepines; D016578:Crack Cocaine; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride