Impaired learning of classically conditioned bradycardia in rats following fourth ventricle administration of D-Ala2-methionine-enkephalinamide.

Prior to differential classical conditioning on two successive days, three groups of rats received an infusion (10 micrograms) of either the opioid peptide D-alanine2-methionine-enkephalinamide (DALA), DALA plus naltrexone (5 micrograms), or saline into the rostral region of the fourth ventricle. A fourth group, which served as a control to help localize DALA's site of action, received an infusion of DALA (10 micrograms) into the brain stem area on the floor of the ventricle. The group given DALA alone in the ventricle showed no evidence of a heart rate conditioned response (CR) either during conditioning or during a nondrug test session given 2 days after conditioning. Interference with the CR by DALA was reversed by the concomitant infusion of naltrexone. The control group given DALA in the brain stem developed a normal CR. It was suggested that DALA-induced opioid-receptor activity in the region of the periaqueductal/periventricular gray or locus coeruleus region of the ventricle may have prevented the learning of a CR. This could have occurred through a blunting of the emotional aftereffects of the unconditioned stimulus or through interference with projection pathways to other areas.