Chronic and intra-amygdala administrations of the ACTH(4-9) analog ORG 2766 modulate behavioral changes after manipulation of NMDA-receptor activity.

Microinjection of N-methyl-D-aspartic acid (NMDA, 300 ng/3 microliters) into the left lateral ventricle causes a substantial increase in locomotor activity which can be significantly reduced by a chronic pretreatment with the ACTH(4-9) analogue ORG 2766(1 microgram/0.5 ml saline, subcutaneous (s.c.) every day for 7 days, last injection 24 h before the NMDA-injection). A single dose of ORG 2766 (1 ng/1 microliter) injected into the left central amygdaloid nucleus 30 min before the NMDA-injection was equally effective in reducing the increase in locomotion. Furthermore it counteracted the predominance of contralateral turning induced by the NMDA-injection. The data give support for the idea that ORG 2766 excerts its effects on behavior and neural recovery by modulating NMDA receptor activity in the brain.