Effect of chronic naltrexone administration and its withdrawal on the regional activity of neurons that contain norepinephrine, dopamine and serotonin.
A method is described that permits the simultaneous quantitation of norepinephrine (NE), dopamine (DA) serotonin (5-HT) and their respective major metabolites, 3-methoxy-4-hydroxy phenylglycol (MHPG), 3-methoxytyramine (3-MT), dihydroxyphenyl acetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) in discrete brain regions. The ratio of MHPG/NE, DOPAC/DA and 5-HIAA/5-HT was used to assess the effects of the chronic administration of the narcotic antagonist, naltrexone, and its withdrawal on the regional activity of neurons that contain NE, DA and 5-HT respectively. Chronic administration of naltrexone (8 days) is associated with a significant increase in the ratio of 5-HIAA/5-HT and DOPAC/DA in the frontal cortex and dorsal hippocampus respectively. Under this condition the thalamic concentration of 3-MT in 4 of 8 animals is also significantly elevated. In contrast, the mesolimbic forebrain exhibited a decrease in the MHPG/NE ratio (4 out of 8 animals). One day following naltrexone pellet removal the above ratios, as well as the mean content of 3-MT in the thalamus, returned to control values. At this time the content of 3-MT in the thalamus (5 of 5 animals) and frontal cortex (3 of 9 rats) was appreciably elevated, while its content in the dorsal hippocampus was significantly reduced (6 of 9 rats). These data suggest that the activity of several central monoaminergic neuronal systems are regulated by an opioid input that is tonically active.
Sharma
T R
TR
Department of Biochemistry, State University of New York, Brooklyn 11203.
Chan
W C
WC
Gintzler
A R
AR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D009271:Naltrexone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome
D012701:Serotonin; D009271:Naltrexone; D004298:Dopamine; D009638:Norepinephrine