EFFECTS OF THE PUTATIVE DOPAMINE D-3 RECEPTOR AGONIST 7-OH-DPAT IN RHESUS-MONKEYS TRAINED TO DISCRIMINATE COCAINE FROM SALINE

These studies were designed to evaluate the effects of the putative do pamine D-3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT), alone and in combination with cocaine, in four rhesus mo nkeys trained to discriminate cocaine (0.4 mg/kg, IM) from saline unde r a fixed-ratio 30 schedule of food presentation. Under these conditio ns, cumulative doses of cocaine (0.013-1.3 mg/kg) produced a dose-depe ndent and complete generalization to the training dose of cocaine in a ll monkeys, while producing only minimal effects on response rates. Th e discriminative stimulus effects of cocaine were antagonized by the n on-selective dopamine receptor antagonist flupenthixol (0.018 mg/kg, I M) in all four monkeys. The effects of 7-OH-DPAT (0.01-1.8 mg/kg) were inconsistent across monkeys. In two of the four monkeys (monkeys L990 and L958), 7-OH-DPAT consistently and completely generalized to cocai ne and decreased response rates in a dose-dependent manner. Both the c ocaine-like discriminative stimulus effects and rate-decreasing effect s of 7-OH-DPAT were antagonized by flupenthixol in these two monkeys. Pretreatment with low doses of 7-OH-DPAT (0.01-0.032 mg/kg) had no eff ect on the cocaine dose-effect curve in monkeys L990 and L958; however , higher doses of 7-OH-DPAT (0.032-0.32 mg/kg) shifted the cocaine dos e-effect curve to the left. In the other two monkeys (monkeys 150F and 89B036), 7-OH-DPAT produced a dose-dependent decrease in response rat es but did not consistently generalize to cocaine. Flupenthixol did no t antagonize the rate-decreasing effects of 7-OH-DPAT in these two mon keys, and pretreatment with 7-OH-DPAT (0.1-0.32 mg/kg) produced a decr ease in response rates but had no effect on the cocaine dose-effect cu rve. Time-course experiments revealed that 7-OH-DPAT (0.32 mg/kg) disp layed a slower onset and a longer duration of effect than the training dose of cocaine. Finally, the D-3/D-2 dopamine agonist quinpirole com pletely generalized to cocaine in three monkeys, and partially in the fourth monkey. Quinpirole showed the highest potency in those monkeys in which 7-OH-DPAT consistently generalized to cocaine. The results of the present study suggest that, in rhesus monkeys, 7-OH-DPAT produces cocaine-like effects and may modulate the discriminative stimulus eff ects of cocaine in some monkeys.