Increase of neurotensin content elicited by neuroleptics in nucleus accumbens.

Abstract

The content of neurotensin immunoreactive material (neurotensin-IR) of nucleus accumbens increases 16 hr after a single injection of 2 mg/kg i.p. of haloperidol; this increase persists for 8 hr or longer. Repeated injections of 2 mg/kg/day of haloperidol i.p. cause a gradual and progressive increase of neurotensin-IR. From 0.32 pmol/mg of protein, it increases to 0.57 pmol/mg (1 week) to 0.62 pmol/mg (2 weeks) and reaches 0.68 pmol/mg (3 weeks). A significant increase of neurotensin-IR content of nucleus accumbens is obtained with 0.5 mg/kg i.p. daily for 2 weeks. Maximal responses are obtained with 1 mg/kg/day in 3 weeks. The striatal neurotensin-IR content of rats injected for 2 weeks with 1 mg/kg/day of haloperidol is also increased. In these rats, the neurotensin-IR content of preoptic area hypothalamus, septum and amygdala failed to increase. The increase of neurotensin-IR material of nucleus accumbens was elicited also by chloropromazine (6 mg/kg), trifluoroperazine (2 mg/kg) and pimozide (1.5 mg/kg) while promazine (10 mg/kg) and promethazine (25 mg/kg) were ineffective. The increase of neurotensin-IR content caused by haloperidol chloropromazine, trifluoroperazine and pimozide in accumbens and striatum suggests a modulation of neurotensin metabolism, synthesis or utilization directly or indirectly through dopaminergic synapses.