Opioid systems in the amygdala can serve as substrate for the behavioral effects of the ACTH-(4-9) analog ORG 2766.

Rats housed individually for 7 days showed a marked decrease in motor activity when tested under intense light conditions in a novel environment as compared to group-housed rats tested under low light conditions. The ACTH analogue ORG 2766 administered into the amygdala decreased the motor activity of group-housed rats tested under low light conditions and increased the motor activity of 7-days isolated rats tested under intense light conditions (ED50: 1-10 pg). Injection of the peptide into the nucleus accumbens was not effective, suggesting that ORG 2766 affects the integration of sensoric stimuli rather than the specific motor output systems. Pretreatment of the rats with the opiate antagonist naltrexone in the amygdala completely blocked the effect of ORG 2766. A similar blockade of the ORG 2766-induced effect could be induced by pretreatment with endorphin antibody suggesting that the "normalizing" activity of ORG 2766 on environmentally induced behavioral changes is mediated by the release of endogenous opioid peptides.