Neurotensin and neurotensin analogues modify the effects of chronic neuroleptic administration in the rat.

The effects of intracerebroventricular neurotensin and the neurotensin analogues neuromedin N and [D-Trp 11]neurotensin on the behavioural responses to chronic neuroleptic administration were investigated in the rat. Chronic (18 weeks) administration of a low dose (12.5 mg/kg, i.m., every 3 weeks) of fluphenazine decanoate alone failed to elicit the vacuous chewing mouth movements (VCMs) which have previously been reported following higher doses of this drug, but VCMs were seen in neuroleptic-treated animals following the additional administration of neurotensin. A higher dose of fluphenazine (25 mg/kg, i.m., every 3 weeks) greatly increased the VCM response, and this potentiation was suppressed to control levels by [D-Trp11]neurotensin, but unaffected by neuromedin N. These findings suggest that alterations in neurotensin may contribute to the deleterious extrapyramidal effects of long-term neuroleptic administration, and that [D-Trp11]neurotensin may attenuate these effects by blockade of neurotensin receptors within the central nervous system.