EFFECTS OF HALOPERIDOL, QUINELORANE, AND LITHIUM ON REGIONAL NEUROTENSIN NEUROMEDIN-N CONCENTRATIONS - FURTHER EVIDENCE FOR NEUROTENSIN NEUROMEDIN-N DOPAMINE INTERACTIONS
R. Clement et al., EFFECTS OF HALOPERIDOL, QUINELORANE, AND LITHIUM ON REGIONAL NEUROTENSIN NEUROMEDIN-N CONCENTRATIONS - FURTHER EVIDENCE FOR NEUROTENSIN NEUROMEDIN-N DOPAMINE INTERACTIONS, Synapse, 17(4), 1994, pp. 241-246
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
.