A novel neurotensin analog blocks cocaine- and D-amphetamine-induced hyperactivity

Neurotensin is a tridecapeptide that exhibits selective anatomic and neuroc hemical interactions with dopaminergic systems. Since dopaminergic neurotra nsmission underlies many of the behavioral properties of psychostimulants, and since neurotensin has been implicated in modulating dopaminergic neurot ransmitter systems, we tested the effect of our novel neurotensin analog, N T69L (N-methyl-Arg(8),L-Lys(9),L-neo-Trp(11),tert-Leu(12)]neurotensin-(8-13 )), on hyperactivity caused by cocaine and D-amphetamine. Previously, we sh owed that NT69L reduces body temperature, blocks apomorphine-induced climbi ng, and haloperidol-induced catalepsy. In this study, NT69L blocked the hyp eractivity induced by both cocaine and D-amphetamine administered at three different doses each, when this peptide was injected intraperitoneally. The se results provide further evidence for the involvement of the neurotensin system in some of the behavioral properties of psychostimulants and suggest that NT69L may find clinical application in patients who abuse this class of compounds. (C) 2001 Elsevier Science B.V. All rights reserved.