Increased levels of proneurotensin/neuromedin N mRNA in rat striatum and nucleus accumbens induced by 7-OH-DPAT and nafadotride

The D-3, dopamine receptor has been proposed as a potential antipsychotic s ite. In this study the effects of the D-3-preferring compounds 7-OH-DPAT an d nafadotride on levels of proneurotensin/neuromedin N (proNT/N) were asses sed. Adult, male, Sprague-Dawley mts were injected subcutaneously (s.c.) wi th the agonist 7-OH-DPAT (0.1 mg/kg) or antagonist nafadatride (1 ng/kg) at doses previously shown to produce negligible occupancy of D-2, receptors i n vivo. As a posit ive control, an additional group of animals was treated with haloperidal (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 accumbe ns shell. Nafadotrime increased proNT/N mRNA levels in the nucleus accumben s shell and dorsomedial caudate nucleus to levels comparable to those produ ced by haloperidol. Nafadot ride also increased proNT/N mRNA in the anterio r and dorsal caudate but to a lesser extent than haloperidol. These data in dicate that 7-OH-DPAT and nafadotride increase proNT/N mRNA levels in brain areas affected by antipsychotic drugs and suggest fl mf the D-3, receptor may regulate proNT/N mRNA expression in the nucleus accumbens shell. (C) 19 99 American College of Neuropsychopharmacology . Published by Elsevier Scie nce Inc.