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 phenomena were examined: a) the yawning-penile erection syndrome induced by small doses of the dopamine agonists apomorphine and N-propylnorapomorphine (NPA); b) yawning produced by the anticholinesterase physostigmine, and c) stereotyped climbing and sniffing produced by a larger dose of apomorphine. Several doses of the peptide were injected intraventricularly 30 min prior to drug administration. Results indicate that neurotensin markedly decreased yawning and penile erections produced by both apomorphine and NPA. These effects were seen with relatively small doses (0.9-3.75 micrograms). Neurotensin also potently decreased physostigmine-induced yawning with the initial inhibitory effect seen with 50 ng of the peptide. Apomorphine-induced climbing was significantly attenuated with 30.0 and 60.0 micrograms neurotensin, whereas stereotyped sniffing was unaffected, even by doses as large as 120.0 micrograms. These findings suggest that neurotensin might antagonize dopamine autoreceptors and indicate that the peptide possess central anticholinergic activity. Furthermore, these results lend support to the hypothesis that neurotensin's profile of central actions resemble that of atypical neuroleptics.