Enkephalin actions on avoidance conditioning may be related to adrenal medullary function.

The present series of studies was undertaken to better characterize the mechanisms mediating enkephalin actions on avoidance conditioning. Both Leu-and Met-enkephalin administered i.p. in amounts of 1.0 or 10.0 micrograms/kg 5 min before training in an active avoidance task significantly impaired acquisition of the response. Adrenal medullectomy, which removes an endogenous store of enkephalin-like peptides, abolished the effect on avoidance conditioning of 10.0 micrograms/kg of exogenously administered Met- or Leu-enkephalin. Increasing the dose of Leu-enkephalin by 10- or 100-fold restored its behavioral activity in adrenal demedullated rats. However, increasing (10-100-fold) or decreasing (10-fold) the dose of Met-enkephalin did not restore its activity in adrenal demedullated animals. This finding suggests that the impairing actions of the two enkephalins are not produced in the same way, but it is consistent with the interpretation that the adrenal medulla may play a role in mediating the actions of Met- and Leu-enkephalin on active avoidance conditioning.