Withdrawal from repeated morphine sensitizes mice to the striatal dopamine release enhancing effect of acute morphine.
The effects of morphine withdrawal and challenge on the alpha-methyl-rho-tyrosine (alpha MT)-induced depletion of dopamine (DA) as well as on DA metabolism and 3H-SCH 23390 and 3H-spiperone binding were studied in the striata of male mice. Morphine was given s.c. 3 times daily for 5 days followed by 1 to 3 days' withdrawal. The alpha MT-induced DA depletion was retarded in mice withdrawn for 1 day from repeated morphine. At this time point the striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) fell, too. In mice withdrawn for 3 days from morphine neither DA depletion nor DOPAC or HVA concentrations differed from those of control mice. In control mice acute morphine challenge accelerated the DA depletion at the dose 10 mg/kg but not at the dose 30 mg/kg. Both doses elevated striatal DOPAC and HVA. In mice withdrawn from repeated morphine for 1 day acute morphine partially counteracted the withdrawal-induced retardation of DA depletion and elevated striatal DOPAC and HVA clearly less than in control mice. However, in mice withdrawn for 3 days 10 mg/kg of morphine clearly enhanced DA depletion and its effect on striatal HVA was significantly augmented. In these mice as in controls the 30 mg/kg dose did not alter striatal DA depletion and elevated HVA less than in controls. Acute morphine did not alter striatal 3-methoxytyramine (3-MT) concentration in control mice but at the dose 10 mg/kg increased it in mice withdrawn for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Airio
J
J
Department of Pharmacy, University of Helsinki, Finland.
Attila
M
M
Leikola-Pelho
T
T
Ahtee
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects*
D001552:Benzazepines; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D009020:Morphine; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid