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

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 nonselective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence.

Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats

“…It is possible that aripiprazole acts mainly as a dopamine antagonist and produces similar sensitization of the dopamine system. Interestingly, the delta opioid receptor agonist SNC80 decreased cocaine self-administration more potently than it decreased food-maintained responding as an acute treatment, but the reverse was true after chronic treatment (Do Carmo et al 2006). The latter finding suggests that reversal of effects can be seen with treatments acting at various classes of receptors, and that cocaine self-administration is an extremely robust behavior, in laboratory animals as in humans (see also Haney et al 2001 for discussion).…”

Targeting Endogenous Mu- and Delta-Opioid Receptor Systems for the Treatment of Drug Addiction

“…others have reported no effect [13, 109]. Similarly naltrindole has been reported to have no effect, to attenuate cocaine self-administration without affecting other behaviors or to produce non-selective reductions in cocaine self-administration [176–178]. These results suggest that DOPr antagonists are unlikely to be useful as a treatment for cocaine addiction.…”

Endogenous opiates and behavior: 2009

“…Both contingent and noncontingent administration of cocaine increased Pro-DYN, but not Pro-Enk mRNA levels in the C/P, but not in the NAC or central nucleus of the amygdala (1331). Acute and chronic administration of the selective delta opioid agonist SNC80 decreased both cocaine-and foodmaintained responding in rhesus monkeys (288). Context-dependent extinction occurs for both cocaine-and morphine-induced floor preferences (878).…”