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WE have investigated the effects of a dopamine D3 receptor antisense oligodeoxynucleotide (ODN), on neurotensin and dynorphin mRNA levels in rat nucleus accumbens. Intracerebroventricular injections of ODNs were made into the lateral ventricle (5 and 10 [mu]g h-1, for 5 days). Receptor autoradiography of dopamine D2 and D3 receptor subtypes was performed. Dynorphin and neurotensin mRNA levels were evaluated by in situ hybridization. Dopamine D3 receptor levels were significantly decreased in nucleus accumbens shell (NAS) of rats that received the D3 antisense ODN. Dynorphin and neurotensin mRNA levels were also significantly decreased in the NAS after D3 antisense ODN treatments. Our results show that D3 receptors may regulate neuropeptide gene expression and demonstrate that an antisense strategy could be useful to identify molecular targets under control of specific dopamine receptor subtypes.

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