Changes in brain monoamine metabolism during withdrawal from chronic oral self-administration of morphine and in response to a morphine challenge in the withdrawn state.
Although p.o. self-administration of morphine is a reliable and convenient means of inducing physical dependence, its effects on brain monoamine metabolism have not been determined. Accordingly, in the present experiment young Wistar rats drank increasing concentrations (0.1-0.5 mg/ml) of morphine in water, or water alone, for 37 days. Half the rats in each group were challenged with morphine (10 mg/kg s.c.) when 27 to 29 hr withdrawn, and half with saline. Rats were sacrificed 2 hr postinjection. Seven brain regions were analyzed for noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT), and their respective metabolites. In all cases in which a comparison could be made with prior work utilizing repeated injections to produce dependence, the p.o. regimen produced the same effects. Thus, the mode of administration does not seem to modify the response of monoaminergic neurons to chronic morphine. In withdrawal, NA turnover increased but DA and 5-HT turnovers decreased. Acute morphine accelerated the turnover of all three monoamines. The NA response was attenuated in some brain regions of withdrawn rats, indicating the development of tolerance to the turnover-enhancing effect of acute morphine in noradrenergic neurons. In contrast, the effect of acute morphine on cerebral 5-HT turnover was not altered, and its effect on cerebral DA turnover was enhanced in withdrawn rats. Our results suggest that there are fundamental differences among the three monoaminergic systems in their capacities for adapting to chronic morphine treatment.
Ahtee
L
L
Department of Pharmacy, University of Helsinki, Finland.
Attila
L M
LM
Carlson
K R
KR
Haikala
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000284:Administration, Oral; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis; D009020:Morphine / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D001679:Biogenic Amines; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D009020:Morphine; C001746:3-methoxytyramine; D004298:Dopamine