Centrally administered [D-Trp11]neurotensin, as well as neurotensin protected from inactivation by thiorphan, modifies locomotion in rats in a biphasic manner

Neurotensin injected intracerebroventricularly at the dose of 30 ng per rat was without intrinsic effect on locomotion. When associated with the enkephalinase inhibitor thiorphan (50 micrograms, intracerebroventricular) it decreased locomotor activity. On the contrary, the 3 micrograms dose of NT, which had a tendency to decrease locomotion, stimulated locomotor activity when associated with thiorphan (50 micrograms, intracerebroventricular). This effect was independent of endogenous enkephalins since it was not suppressed by a high dose of naloxone (2 mg/kg). Similarly, increasing doses of the enkephalinase-resistant peptide [D-Trp11]neurotensin had a biphasic effect on locomotion since doses lower than 60 ng were hypokinetic whereas higher doses were hyperkinetic. This latter effect was not modified by thiorphan. It was antagonized by the dopamine antagonist haloperidol (50 micrograms/kg, IP).