Effects of the selective delta opioid agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys

Eur J Pharmacol. 2006 Oct 10;547(1-3):92-100. doi: 10.1016/j.ejphar.2006.06.075. Epub 2006 Jul 5.

Abstract

Delta agonists such as SNC80 ((+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) produce some cocaine-like behavioral effects and warrant evaluation as candidate "agonist" medications for cocaine abuse. The present study examined acute and chronic effects of the systemically active delta agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys. Acute SNC80 (0.32-3.2 mg/kg, i.m.) pretreatment dose-dependently decreased cocaine self-administration (0.0032 mg/kg/injection), but doses of SNC80 that decreased cocaine self-administration also decreased food-maintained responding. In chronic studies, SNC80 (0.32-3.2 mg/kg/h, i.v.) was delivered for 7 days, and food or cocaine (0.01 mg/kg/injection) was available during 4 daily components of food availability and 4 daily components of drug availability. Chronic SNC80 (1.8 mg/kg/h) tended to decrease cocaine self-administration but produced greater reductions in food-maintained responding. A higher dose of 3.2 mg/kg/h SNC80 eliminated both cocaine- and food-maintained responding and produced profound sedation in one monkey and was not tested in other monkeys. These findings indicate that SNC80 produced dose-dependent and non-selective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Benzamides / pharmacology*
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / physiopathology
  • Cocaine-Related Disorders / prevention & control
  • Cocaine-Related Disorders / psychology
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Food*
  • Macaca mulatta
  • Male
  • Piperazines / pharmacology*
  • Receptors, Opioid, delta / agonists*
  • Reinforcement Schedule
  • Self Administration
  • Time Factors

Substances

  • Benzamides
  • Piperazines
  • Receptors, Opioid, delta
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Cocaine