EFFECTS OF HALOPERIDOL, QUINELORANE, AND LITHIUM ON REGIONAL NEUROTENSIN NEUROMEDIN-N CONCENTRATIONS - FURTHER EVIDENCE FOR NEUROTENSIN NEUROMEDIN-N DOPAMINE INTERACTIONS

In order to further characterize the pharmacologic mechanisms that med iate the antipsychotic drug-induced increase in neurotensin (NT) in nu cleus accumbens and striatum, the effects of three weeks treatment wit h psychotherapeutic levels of lithium alone or in conjunction with hal operidol were compared to the ability of haloperidol alone to alter NT and neuromedin N (NMN) regional brain concentrations in rats. A separ ate experiment examined the ability of a selective dopamine D-2 recept or agonist, quinelorane, to alter NT/NMN regional concentrations after three weeks of treatment as compared to haloperidol, a D-2 receptor a ntagonist. Haloperidol (1 mg/kg) increased both NT and NMN concentrati ons in several brain regions and these parallel peptide increases were highly correlated. Lithium chloride (0.4 mM) had no effect, either al one or with haloperidol, on NT/NMN concentrations. Quinelorane (1 mg/k g), however, effectively increased both NT and NMN concentrations in t he caudate nucleus and nucleus accumbens, as did haloperidol (2 mg/kg) . These data indicate that the induction of NT and NMN, whose adjacent sequences are contained in a pro-hormone product of a single gene, oc curs in tandem and remains proportional, as well as demonstrating that putative D-2 receptor agonists can produce effects on NT/NMN systems that are similar to D-2 receptor antagonists. (C) 1994 Wiley-Liss, Inc .