Naltrindole, an opioid delta receptor antagonist, blocks cocaine-induced facilitation of responding for rewarding brain stimulation.
Recent experimental results have led to the suggestion that opioid antagonists can modulate the reinforcing properties of cocaine. In this experiment, rats were fixed with chronically indwelling bipolar electrodes for stimulation of the medial forebrain bundle (MFB) as it courses through the hypothalamus. Rats were taught to press a lever for brief trains of electrical stimulation of the MFB. Subsequently, they were allowed to press for varying intensities of stimulation daily until their response rates were stable. Cocaine (5 mg/kg, s.c.) enhanced the rate of pressing for lower intensities of brain stimulation. Naltrindole (3 mg/kg, i.p.) had no effect on response rate alone but blocked the cocaine-induced facilitation of pressing for rewarding brain stimulation. An implication that can be drawn from these data is that naltrindole, or other delta-selective opioid antagonists, might be effective as medicines for use in treating cocaine abuse.
Reid
L D
LD
Department of Psychology, Renssclaer Polytechnic Institute, Troy, NY 12180.
Hubbell
C L
CL
Glaccum
M B
MB
Bilsky
E J
EJ
Portoghese
P S
PS
Porreca
F
F
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003042:Cocaine / Q000037:antagonists & inhibitors*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D012653:Self Stimulation / Q000187:drug effects
D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole; D003042:Cocaine