Differential effect of haloperidol on release of neurotensin in extrapyramidal and limbic systems

The effect of the antipsychotic drug haloperidol on extracellular neurotensin-like immunoreactivity was investigated by microdialysis and compared with the time-dependent response of tissue neurotensin-like immunoreactivity content in brain structures containing dopamine nerve cell bodies and terminals. A single administration of haloperidol (1 mg/kg) increased the extracellular neurotensin-like immunoreactivity levels in nucleus accumbens as measured by microdialysis, but decreased its extracellular concentration in the caudate regions surrounding the probe. The same treatment increased the tissue content of neurotensin-like immunoreactivity in both the nucleus accumbens core and all caudate regions examined within 24 h after the injection. Interestingly, although the neurotensin-like immunoreactivity concentration in the substantia nigra was not altered by the haloperidol treatment, neurotensin-like immunoreactivity levels decreased significantly in the ventral tegmental area. These findings suggest that varied neurotensin systems are associated with nigrostriatal and mesolimbic dopamine pathways and these systems have different responses to haloperidol. The changes in the release of neurotensin may contribute to altered caudate and accumbens neurotensin-like immunoreactivity tissue content induced by haloperidol treatment, but other factors, such as variation in synthesis also likely influence these effects. Differential actions of haloperidol on neurotensin release might be due to regional differences in dopamine or sigma receptor subtypes associated with the neurotensin-containing neurons.