Ontogeny of the effect of antipsychotic drug treatment on neurotensin concentrations in the rat brain.

It has been well documented that treatment with haloperidol and other typical antipsychotic drugs increase neurotensin (NT) concentrations in the nucleus accumbens and caudate nucleus in adult rats. The NT neuronal system has been found to undergo distinct age-related changes in the rat brain, and therefore, it is of interest to examine the ontogeny of the effects of antipsychotic drug treatment on NT concentrations. In order to determine when, or if, antipsychotic drug treatment has an effect on NT-containing neurons in the developing rat, rat pups received a single dose of haloperidol (2.0 mg/kg, s.c.) or vehicle at 9,14, or 20 days after birth. Regional brain NT concentrations were then measured using a sensitive and specific radioimmunoassay. Treatment with haloperidol had no effect on NT concentrations in any brain region in 10-day-old rat pups. At 15 days of age, haloperidol significantly increased NT concentrations in the caudate nucleus (120% of control, P < 0.05). At 21 days of age, haloperidol increased NT concentrations in the caudate nucleus (193% of control, P < 0.001) and nucleus accumbens (126% of control, P < 0.005) similar to that seen in adult animals. There were no statistically significant gender-related differences found in any age or treatment group studied. These findings indicate that there is a specific time point during post-natal development when rat brain NT systems become responsive to antipsychotic drug administration.