TY - JOUR
T1 - BMY 14802, a potential antipsychotic drug, increases expression of proneurotensin mRNA in the rat striatum
AU - Levant, Beth
AU - Merchant, Kalpana M.
AU - Dorsa, Daniel M.
AU - Nemeroff, Charles B.
N1 - Funding Information:
Acl~owledgcmen~. We are grateful to Dr. Duncan Taylor of Bristol-Myers Co. for generouslys upplying the BMY 14802. Supported by NIMH MH-39415 (B.L., C.B.N.), the Department of Veterans Affairs Research Service, NS20311 (D.M.D.), and the Washington Institute for Mental Illness Research and Training (K.M.M., D.M.D.).
PY - 1992/2
Y1 - 1992/2
N2 - 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 increse in NT biosynthesis as assessed by the level of expression of proNT mRNA. The potential antipsychotic drug and σ receptor ligand BMY 14802 has been shown to produce increases in the concentration 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 caudat. Labeling was most intense in the dorsal caudate. NT concentrations were unaltered at this time point. Eighteen hours after injection, significant increases in NT concentrations 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.
AB - 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 increse in NT biosynthesis as assessed by the level of expression of proNT mRNA. The potential antipsychotic drug and σ receptor ligand BMY 14802 has been shown to produce increases in the concentration 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 caudat. Labeling was most intense in the dorsal caudate. NT concentrations were unaltered at this time point. Eighteen hours after injection, significant increases in NT concentrations 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.
KW - Antipsychotic
KW - BMY 14802
KW - Neurotensin
KW - Proneurotensin mRNA
KW - Striatum
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U2 - 10.1016/0169-328X(92)90130-4
DO - 10.1016/0169-328X(92)90130-4
M3 - Article
C2 - 1349718
AN - SCOPUS:0026505411
SN - 0169-328X
VL - 12
SP - 279
EP - 284
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 4
ER -