Effects of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on cocaine choice in cynomolgus monkeys

Drugs that alter brain serotonin (5-HT) function can modulate the behavioral effects of cocaine, but the underlying receptor mechanisms are poorly understood. The present study examined the effects of the selective 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.1 mg/kg, i.v.) on cocaine self-administration in the context of a choice procedure. Five adult male cynomolgus monkeys self-administered cocaine (saline, 0.003-0.03 mg/kg per injection) under a concurrent fixed-ratio 50 schedule of food (1-g banana-flavored pellets) and cocaine presentation. Allocation of responses to the cocaine-associated lever (cocaine choice) increased in a dose-related manner from < or =20% of total responses when saline or 0.003 mg/kg per injection cocaine was the alternative to food to > or =75% when 0.03 mg/kg per injection cocaine was available. In four of five monkeys, when choice was between a low cocaine dose and food, 0.01 mg/kg 8-OH-DPAT increased injection-lever responding. At cocaine doses which occasioned > or =75% cocaine choice, 8-OH-DPAT did not alter response allocation. In the fifth monkey, 8-OH-DPAT only decreased injection-lever responding. When choice was between saline and food, 8-OH-DPAT did not reliably shift responding to the injection lever, except at doses that disrupted operant performance. These results suggest that a 5-HT1A receptor agonist can increase the reinforcing strength of a low cocaine dose relative to a concurrently available non-drug reinforcer.

Assessment of the relative reinforcing strength of cocaine in socially housed monkeys using a choice procedure.

Position in the social hierarchy can influence brain dopamine function and cocaine reinforcement in nonhuman primates during early cocaine exposure. With prolonged exposure, however, initial differences in rates of cocaine self-administration between dominant and subordinate monkeys dissipate. The present studies used a choice procedure to assess the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys with extensive cocaine self-administration histories. Responding was maintained under a concurrent fixed-ratio 50 schedule of food and cocaine (0.003-0.1 mg/kg per injection) presentation. Responding on the cocaine-associated lever increased as a function of cocaine dose in all monkeys. Although response distribution was similar across social rank when saline or relatively low or high cocaine doses were the alternative to food, planned t tests indicated that cocaine choice was significantly greater in subordinate monkeys when choice was between an intermediate dose (0.01 mg/kg) and food. When a between-session progressive-ratio procedure was used to increase response requirements for the preferred reinforcer (either cocaine or food), choice of that reinforcer decreased in all monkeys. The average response requirement that produced a shift in response allocation from the cocaine-associated lever to the food-associated lever was higher in subordinates across cocaine doses, an effect that trended toward significance (p = 0.053). These data indicate that despite an extensive history of cocaine self-administration, most subordinate monkeys were more sensitive to the relative reinforcing strength of cocaine than dominant monkeys.

Putting the coke in coke

The story of cocaine: from royalty to popular refresher... Surprising as it sounds, Coca Cola gets its name from one of its original ingredients - cocaine. And although the drug's now illegal, this wasn't always the case. But how did it become popular, what led to its downfall, and how does Coca Cola come in to it?