FURTHER-STUDIES ON THE MODULATION OF REGIONAL BRAIN NEUROTENSIN CONCENTRATIONS BY ANTIPSYCHOTIC-DRUGS - FOCUS ON HALOPERIDOL AND BMY-14802

Acute and chronic treatment with the antipsychotic drug haloperidol or the potential antipsychotic BMY 14802 produce increases in regional neurotensin concentrations which are similar with respect to regional specificity (nucleus accumbens and caudate), time course, magnitude of increase and precedence by an increase in proneurotensin mRNA. The present study characterizes further the effects of haloperidol and BMY 14802 on regional brain neurotensin concentrations and compares certain of their effects to those of sulpiride. Neurotensin concentrations in discrete brain regions of adult, male, Sprague-Dawley rats were determined by radioimmunoassay. Both acute and chronic treatment with BMY 14802 produced significant decreases in the concentration of neurotensin in the frontal cortex. When administered concomitantly, low doses of haloperidol and BMY 14802 produced additive increases in neurotensin content in the nucleus accumbens and caudate. Increases in neurotensin content resulting from concomitant treatment, or with doses which produce maximal effects individually, were not greater than those produced by either drug alone. Concomitant administration of SCH 23390 and sulpride attenuated the neurotensin increases observed after treatment with sulpiride. Increases in neurotensin concentrations produced by haloperidol and BMY 14802 were not antagonized by SCH 23390. These findings support the hypothesis that haloperidol and BMY 14802 modulate regional neurotensin concentrations through a common or similar mechanism which is distinct from that of sulpiride.