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.
Levant
B
B
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Garimelli
B
B
Shafer
R A
RA
Merchant
K M
KM
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009496:Neurotensin / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009281:Naphthalenes; D010446:Peptide Fragments; D011498:Protein Precursors; D011759:Pyrrolidines; D013764:Tetrahydronaphthalenes; C052457:neuromedin N precursor; C042090:neuromedin N; D009496:Neurotensin; D006220:Haloperidol; C097285:nafadotride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin