Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone.
Rats, fixed with chronically indwelling electrodes for electrical intracranial stimulation (ICS) of the lateral hypothalamus, were taught to press a bar for ICS. Once pressing rates became stable, during daily 20-min sessions, rats were given cocaine (5 or 20 mg/kg) before the sessions. When given daily, cocaine consistently enhanced rates of pressing. When a combination of small doses of isradipine (e.g., 1 mg/kg) and naltrexone (3 mg/kg) were given before cocaine administration. the combination blocked cocaine's enhancement of pressing for ICS. The combination, however, neither reduced rates of pressing below those observed under placebos (i.e., baseline conditions) nor reduced rates when no cocaine was given. Naltrexone and isradipine (in the dose used in the combination) by themselves did not block cocaine's effects. This profile of effects indicates that a combination of isradipine and naltrexone is apt to be useful in treating cocaine use disorders.
Pabello
N G
NG
Laboratory for Psychopharmacology, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
Hubbell
C L
CL
Cavallaro
C A
CA
Barringer
T M
TM
Mendez
J J
JJ
Reid
L D
LD
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D005473:Fluoxetine / Q000627:therapeutic use; D017275:Isradipine / Q000627:therapeutic use*; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D014635:Valproic Acid / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D009292:Narcotic Antagonists; D005473:Fluoxetine; D009271:Naltrexone; D014635:Valproic Acid; D017275:Isradipine