EFFECT OF AUTOANALGESIA ON CNS ENKEPHALIN RECEPTORS

Fear conditioning to foot shock (15 sec/day, 12 days) elicited autoanalgesia in 10 male (Sprague Dawley) rats, while 17 non-shock control rats exhibited no analgesia as measured by the tail-flick assay. The binding of 3H-leu-enkephalin to synaptosomal preparations isolated from fear conditioned (experimental) and control animals was analyzed. At leu-enkephalin concentrations of 10-9 M or less, both synaptosomal preparations demonstrated high affinity binding with dissociation constants on the order of 10-10. Binding of leu-enkephalin could not be displaced by a hundred-fold excess of naloxone at leu-enkephalin concentrations less than 10-9 M. However, the ability of naloxone to compete with leu-enkephalin for binding sites progressively increased at concentrations greater than 10-9 M leu-enkephalin. At these ligand concentrations, the competition of naloxone for leu-enkephalin binding sites was more dramatic in the control than in the experimental animals. These data support the existence of two classes of receptors for leu-enkephalin, one of which is not blocked by opiate antagonists. Furthermore, changes in binding capacity associated with autoanalgesia produced by conditioned fear are consistent with the hypothesis of endogenous release of opiate-like peptides in response to stress. © 1979.