Autoregulation of dopamine synthesis in subregions of the rat nucleus accumbens.
The discovery of a core-shell dichotomy within the nucleus accumbens has opened new lines of investigation into the neuronal basis of psychiatric disorders and drug dependence. In the present study, the autoregulation of dopamine synthesis in subdivisions of the rat nucleus accumbens was examined. We measured the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) after the inhibition of aromatic L-amino acid decarboxylase with 3-hydroxylbenzylhydrazine (NSD-1015, 100 mg kg(-1)) as an in vivo index of dopamine synthesis. The effect of the dopamine D(1)/D(2) receptor agonist apomorphine (0, 20, 100, 500 microgram kg(-1)) and the dopamine D(2)/D(3) receptor agonist quinpirole (0, 20, 100, 500 microgram kg(-1)) on dopamine synthesis was determined in the dorsolateral core, ventromedial shell, and rostral pole of the nucleus accumbens. DOPA accumulation was also measured in the frontal cortex, olfactory tubercle, and caudate nucleus of the same rats for comparative purposes. The results show that the three sectors of the nucleus accumbens had similar basal levels of DOPA. Both apomorphine and quinpirole produced a decrease in the dopamine synthesis rate in all brain regions examined. In general, the dopamine D(2)/D(3) receptor agonist quinpirole produced a significantly greater decrease in DOPA accumulation than the dopamine D(1)/D(2) receptor agonist apomorphine. Within the nucleus accumbens, we found no core-shell differences in the agonist-induced suppression of dopamine synthesis, but the rostral pole was less sensitive to the highest dose of both dopamine agonists. These results suggest that differences in dopamine function between the core and shell might not involve region-specific differences in the receptor-mediated autoregulation of dopamine neurotransmission. Moreover, the blunted effect of dopamine agonists in the rostral pole illustrates that this region of the accumbens is functionally distinct, possibly due to a lower dopamine receptor reserve when compared to the core and shell.
Heidbreder
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CA
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Building H25, Room 104A, Essex CM19 5AW, Harlow, UK.  Christain_A_heidbreder@sbphrd.com
Baumann
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MH
D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018491:Dopamine Agonists; D019257:Quinpirole; D004295:Dihydroxyphenylalanine; D001058:Apomorphine; D004298:Dopamine