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

Behav Pharmacol. 2005 May;16(3):187-91. doi: 10.1097/00008877-200505000-00008.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology
  • Dopamine Uptake Inhibitors / pharmacology*
  • Macaca fascicularis
  • Male
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Reinforcement, Psychology
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Dopamine Uptake Inhibitors
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cocaine