title: Effects of olanzapine on extracellular concentrations and tissue content of neurotensin in rat brain regions.
abstract: We have previously shown that both the psychostimulant d-amphetamine and the antipsychotics haloperidol and risperidone affect extracellular concentrations and tissue content of neurotensin (NT) in distinct brain regions. This study investigated the effects of acute olanzapine (1, 5mg/kg, s.c.) on extracellular NT-like immunoreactivity (-LI) concentrations in the ventral striatum (vSTR) and the medial prefrontal cortex (mPFC), and the effects of acute d-amphetamine (1.5mg/kg, s.c.) on extracellular NT-LI in these brain regions after a 30-day olanzapine (15mg/kg, p.o.) administration in rats. The effects of a 30-day olanzapine (3, 15mg/kg, p.o.) administration and d-amphetamine (1.5mg/kg, s.c.) coadministration during either the last day (acute) or the last 8days (chronic) on NT-LI tissue content in distinct rat brain regions were also studied. Acute olanzapine increased extracellular NT-LI, in both the vSTR and the mPFC. Chronic olanzapine increased and decreased basal extracellular NT-LI in the vSTR and the mPFC, respectively, and abolished the stimulatory effects of acute d-amphetamine on extracellular NT-LI in these brain regions. Chronic olanzapine as well as acute and chronic d-amphetamine affected NT-LI tissue content in a brain region-dependent manner. Chronic olanzapine prevented the effects of acute and chronic d-amphetamine on NT-LI tissue content in certain brain regions. The fact that olanzapine and d-amphetamine affected extracellular NT-LI in the vSTR and mPFC as well as NT-LI tissue content in distinct brain regions further supports the notion that NT plays a role in the therapeutic actions of antipsychotic drugs and possibly also in the pathophysiology of schizophrenia.
authors.affiliation: Institution of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Huddinge University Hospital, Sweden.
authors.forename: Susanne H M
authors.initials: SH
authors.lastname: Gruber
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
authors.forename: George G
authors.initials: GG
authors.lastname: Nomikos
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009496:Neurotensin / Q000378:metabolism*; D000077152:Olanzapine; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D001569:Benzodiazepines; D009496:Neurotensin; D000077152:Olanzapine