BMY 14802, a potential antipsychotic drug, increases expression of proneurotensin mRNA in the rat striatum.
Treatment with efficacious antipsychotic drugs, such as haloperidol, increases the concentrations of neurotensin (NT) in the nucleus accumbens and caudate nucleus of the rat. The increases in NT content produced by haloperidol have been shown to be associated with an increase in NT biosynthesis as assessed by the level of expression of proNT mRNA. The potential antipsychotic drug and sigma receptor ligand BMY 14802 has been shown to produce increases in the concentrations of NT in the nucleus accumbens and caudate that are similar to those produced by haloperidol with respect to the magnitude of the increases and the time course over which they occur. This study evaluated the effects of BMY 14802 on the expression of proNT mRNA and NT concentration in the rat striatum. Three hours after a single injection of BMY 14802 (35 mg/kg, i.p.) expression of proNT mRNA was significantly increased in the nucleus accumbens and caudate. Labeling was most intense in the dorsal caudate. NT concentrations were unaltered at this time point. Eighteen hours after injection, significant increases in NT concentration in the nucleus accumbens and caudate were detected. At this time, expression of proNT mRNA was substantially reduced compared to 3 h after treatment although labeling of the dorsal and medial caudate was still greater than that observed in controls.
Department of Pharmacology, Duke University Medical Center, Durham, NC.
B
B
Levant
K M
KM
Merchant
D M
DM
Dorsa
C B
CB
Nemeroff
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001921:Brain / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D007106:Immune Sera; D008297:Male; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D009928:Organ Specificity; D011498:Protein Precursors / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu
D014150:Antipsychotic Agents; D007106:Immune Sera; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D011498:Protein Precursors; D011743:Pyrimidines; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D009496:Neurotensin