Effects of CI-943, a potential antipsychotic drug, and haloperidol on regional brain neurotensin concentrations

Abstract

Treatment with efficacious antipsychotic drugs such as haloperidol increases the concentrations of neurotensin (NT) in the nucleus accumbens and caudate nucleus of the rat. These increases in NT concentrations may be associated with the therapeutic and/or side effects of these drugs. CI-943, a novel compound without appreciable affinity for dopamine-binding sites, produces behavioral effects in animals, which suggest that it may possess antipsychotic activity. This study evaluated the effects of subchronic treatment (3 weeks) with CI-943 or haloperidol on regional brain NT concentrations in rats. Haloperidol treatment (1 mg/kg) produced significant increases in the concentrations of NT in the nucleus accumbens and caudate nucleus but not in the other brain regions studied. Like haloperidol, CI-943 (40 mg/kg) increased NT concentrations in the nucleus accumbens and caudate but differed in that CI-943 produced significantly greater increases in NT concentration in the caudate than haloperidol and also increased NT content in the substantia nigra/ventral tegmental area and hypothalamus. The regional specificity of the NT alterations produced by chronic treatment with CI-943, a nondopamine receptor ligand, was similar to that previously reported after treatment with multiple doses of methamphetamine.