ATYPICAL NEUROLEPTIC-LIKE BEHAVIORAL-EFFECTS OF NEUROTENSIN

To better characterize the neuroleptic-like properties of neurotensin, the dose-related effects of the peptide on the following behavioral p henomena were examined: a) the yawning-penile erection syndrome induce d by small doses of the dopamine agonists apomorphine and N-propylnora pomorphine (NPA); b) yawning produced by the anticholinesterase physos tigmine, and c) stereotyped climbing and sniffing produced by a larger dose of apomorphine. Several doses of the peptide were injected intra ventricularly 30 min prior to drug administration. Results indicate th at neurotensin markedly decreased yawning and penile erections produce d by both apomorphine and NPA. These effects were seen with relatively small doges (0.9-3.75 mug). Neurotensin also potently decreased physo stigmine-induced yawning with the initial inhibitory effect seen with 50 ng of the peptide. Apomorphine-induced climbing was significantly a ttenuated with 30.0 and 60.0 mug neurotensin, whereas stereotyped snif fing was unaffected, even by doses as large as 120.0 mug. These findin gs suggest that neurotensin might antagonize dopamine autoreceptors an d indicate that the peptide possesses central anticholinergic activity . Furthermore, these results lend support to the hypothesis that neuro tensin's profile of central actions resemble that of atypical neurolep tics.