History of cocaine self-administration alters morphine reinforcement in the rat.
It has been shown repeatedly that cocaine pre-exposure may sensitise neurochemical and behavioural responses to opioid drugs. The aim of the present study was to investigate effects of a prior history of cocaine self-administration on morphine reinforcement in the rat. Male Sprague-Dawley rats were allowed to acquire intravenous cocaine self-administration (0.3 mg/kg/infusion) for 20 days. When operant responding for cocaine had stabilised, morphine was introduced instead of cocaine in the next self-administration session. One group of cocaine-exposed rats was allowed to respond for 0.56 mg/kg/infusion of morphine (i.e. the dose which was willingly self-administered by drug-naive controls). The second group was allowed to respond for 0.056 mg/kg/infusion of morphine (i.e. the dose which did not maintain self-administration behaviour in the drug-naive rats). The subjects with the history of cocaine self-administration, in contrast to the drug-naive group, did not maintain operant responding for 0.56 mg/kg/infusion of morphine. These rats easily self-administered the ten times lower dose of the opioid (0.056 mg/kg/infusion). An opioid receptor antagonist, naltrexone (1 mg/kg i.p.) restored the positive reinforcing properties of the higher dose of morphine in the cocaine-exposed rats. Concluding, the present results suggest that prior history of cocaine self-administration sensitises rats to the positive reinforcing properties of morphine.
Mierzejewski
Pawel
P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Sobieskiego 9 St., 02-957 Warsaw, Poland. mierzeje@ipin.edu.pl
Stefanski
Roman
R
Bienkowski
Przemyslaw
P
Kostowski
Wojciech
W
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009271:Naltrexone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D009020:Morphine; D003042:Cocaine