Increased levels of proneurotensin/neuromedin N mRNA in rat striatum and nucleus accumbens induced by 7-OH-DPAT and nafadotride.
The D3 dopamine receptor has been proposed as a potential antipsychotic site. In this study, the effects of the D3-preferring compounds 7-OH-DPAT and nafadotride on levels of proneurotensin/neuromedin N (proNT/N) were assessed. Adult, male, Sprague-Dawley rats were injected subcutaneously (s.c.) with the agonist 7-OH-DPAT (0.1 mg/kg) or antagonist nafadotride (1 mg/kg) at doses previously shown to produce negligible occupancy of D2 receptors in vivo. As a positive control, an additional group of animals was treated with haloperidol (3 mg/kg, s.c.). ProNT/N mRNA levels were determined by in situ hybridization. 7-OH-DPAT increased proNT/N mRNA in the nucleus accumbens shell. Nafadotride increased proNT/N mRNA levels in the nucleus accumbens shell and dorsomedial caudate nucleus to levels comparable to those produced by haloperidol. Nafadotride also increased proNT/N mRNA in the anterior and dorsal caudate but to a lesser extent than haloperidol. These data indicate that 7-OH-DPAT and nafadotride increase proNT/N mRNA levels in brain areas affected by antipsychotic drugs and suggest that the D3 receptor may regulate proNT/N mRNA expression in the nucleus accumbens shell.[1]References
- Increased levels of proneurotensin/neuromedin N mRNA in rat striatum and nucleus accumbens induced by 7-OH-DPAT and nafadotride. Levant, B., Garimelli, B., Shafer, R.A., Merchant, K.M. Neuropsychopharmacology (1999) [Pubmed]
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