Effects of repeated morphine on cerebral dopamine release and metabolism in AA and ANA rats.
Cerebral dopaminergic mechanisms were studied in the nucleus accumbens and caudate-putamen of alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Non-Alcohol) rats after 4-day repeated morphine treatment. This treatment has been shown to enhance the locomotor activity stimulating effect of morphine in the AA but not in the ANA rats. Morphine (1 or 3 mg/kg) or saline was administered subcutaneously once daily and the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured, in freely moving rats by in vivo microdialysis on days 1 and 4. Morphine increased accumbal DA, DOPAC and HVA similarly in rats of both lines, and no sensitization of DA release or metabolism was seen in rats of either line given morphine repeatedly. In the caudate-putamen, morphine increased DA, DOPAC and HVA significantly only in the AA rats. During repeated treatment, the morphine-induced elevation of DA metabolites, but not that of DA, was enhanced similarly in rats of both lines. These results suggest that the effects of acute morphine administration on nigrostriatal dopaminergic mechanisms are stronger in the AA than in the ANA rats, whereas the effects of morphine on mesolimbic dopaminergic systems do not differ. Furthermore, in rats of both lines, repeated morphine treatment enhanced the responses of the nigrostriatal dopaminergic systems similarly, but no enhancement occurred in the mesolimbic systems of rats of either line. These findings do not support the critical role of accumbal dopaminergic systems in morphine-induced behavioural sensitization.
Mikkola
J A
JA
Department of Pharmacy, Division of Pharmacology and Toxicology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
Honkanen
A
A
Piepponen
T P
TP
Kiianmaa
K
K
Ahtee
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D000701:Analgesics, Opioid; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; D004298:Dopamine; D006719:Homovanillic Acid