Possible involvement of the central nervous system in long-term effect of caerulein on amphetamine-induced hyperactivity in rats.

The present experiments were performed in order to ascertain whether the long-term antagonistic effect of caerulein on amphetamine-induced hyperactivity is produced in the central nervous system. In the vagotomized rats, animals treated with a combination of caerulein and haloperidol and exposed to amphetamine on the 1st day became less sensitive to amphetamine for 24 hr to 1 week when their ambulatory activities were measured in an open field apparatus. The same results were also observed in the experiments where caerulein was applied directly into the lateral ventricle. However, the animals given caerulein in the nucleus accumbens showed no reduced susceptibility to amphetamine. Thus, the present results suggest that caerulein may indirectly modulate some dopaminergic activity in the central nervous system. One possible mechanism involved in the antagonistic effect of caerulein on amphetamine-induced hyperactivity is changes in activities of endocrine systems.