neuromedin-n and Schizophrenia

Evidence implicating neural circuits that utilize the neuropeptide transmitter neurotensin (NT) in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs has previously been reviewed. The majority of evidence, taken together, supports the development of NT receptor agonists as novel antipsychotic drugs. This review comprehensively describes the NT receptor subtypes, discusses the development of NT receptor agonists and the behavioral effects of currently available NT receptor agonists. The compilation of data suggests that NT receptor agonists may represent a novel class of antipsychotic drugs for the treatment of schizophrenia.

Topics: Animals; Antipsychotic Agents; Brain; Drug Design; Humans; Neural Pathways; Neurotensin; Peptide Fragments; Peptides; Receptors, Neurotensin; Schizophrenia

A human genomic clone encompassing exons 1-3 of the neurotensin/neuromedin N gene was identified using a canine neurotensin complementary DNA probe. Sequence comparisons revealed that the 120-amino acid portion of the precursor sequence encoded by exons 1-3 is 89% identical to previously determined cow and dog sequences and that the proximal 250 bp of 5' flanking sequences are strikingly conserved between rat and human. The 5' flanking sequence contains cis-regulatory sites required for the induction of neurotensin/neuromedin N gene expression in PC12 cells, including AP1 sites and two cyclic adenosine-5'-monophosphate response elements. Oligonucleotide probes based on the human sequence were used to examine the distribution of neurotensin/neuromedin N messenger RNA in the ventral mesencephalon of schizophrenics and age- and sex-matched controls. Neurotensin/neuromedin N messenger RNA was observed in ventral mesencephalic cells some of which also contained melanin pigment or tyrosine hydroxylase messenger RNA. Neurons expressing neurotensin/neuromedin N messenger RNA were observed in the ventral mesencephalon of both schizophrenic and non-schizophrenic humans.

Topics: Adult; Aged; Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA Probes; Exons; Female; Gene Expression; Humans; Male; Mesencephalon; Middle Aged; Molecular Sequence Data; Neurotensin; Oligonucleotide Probes; Peptide Fragments; Rats; Reference Values; Restriction Mapping; RNA, Messenger; Schizophrenia; TATA Box