Neurochemical predisposition to self-administer morphine in rats

Using in vivo microdialysis, this study attempted to determine whether a neurochemical predisposition to self-administer morphine could be identified. Extracellular levels of dopamine and its metabolites were measured bilaterally in the mesocorticolimbic and nigrostriatal systems of naive rats that...

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Bibliographic Details
Published in:	Brain research Vol. 578; no. 1-2; p. 215
Main Authors:	Glick, S D, Merski, C, Steindorf, S, Wang, S, Keller, R W, Carlson, J N
Format:	Journal Article
Language:	English
Published:	Netherlands 24-04-1992
Subjects:	3,4-Dihydroxyphenylacetic Acid - metabolism Animals Cerebral Cortex - metabolism Corpus Striatum - metabolism Female Homovanillic Acid - metabolism Hydroxyindoleacetic Acid - metabolism Injections, Intravenous Morphine - administration & dosage Morphine Dependence - physiopathology Nucleus Accumbens - metabolism Rats Rats, Inbred Strains Self Administration Substantia Nigra - metabolism
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Summary:	Using in vivo microdialysis, this study attempted to determine whether a neurochemical predisposition to self-administer morphine could be identified. Extracellular levels of dopamine and its metabolites were measured bilaterally in the mesocorticolimbic and nigrostriatal systems of naive rats that were subsequently trained to self-administer morphine intravenously. There were several significant relationships between dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and rates of morphine self-administration during both acquisition and asymptotic phases of testing. DOPAC and HVA levels in the striatum were inversely correlated with self-administration rates during the asymptotic phase whereas hemispheric asymmetries in striatal metabolite levels were inversely correlated with self-administration during the acquisition phase. DOPAC and HVA levels in in the right but not in the left side of the medial prefrontal cortex were positively correlated with self-administration rates during the acquisition phase; right/left asymmetries in cortical metabolite levels were also correlated with acquisition rates. There were no significant relationships between neurochemical indices and rates of bar-pressing for water. These results suggest that the normal variability in drug seeking behavior is at least in part attributable to individual differences in the organization and activity of brain dopamine systems. Furthermore, different mechanisms appear to be responsible for the initiation and maintenance of morphine intake: DA release in the nucleus accumbens appears to be a critical component of both mechanisms; DA release in the striatum appears to modulate maintenance and, in relationship to striatal lateralization, modulate initiation; DA release in the right but not in the left medial prefrontal cortex appears to be an important predictor of initiation.
ISSN:	0006-8993
DOI:	10.1016/0006-8993(92)90250-D