Roles of delta and mu opioid receptors in mediating the effects of enkephalins on avoidance conditioning.

The effects on one-way active avoidance conditioning of pre-training, systemic administration of the selective mu-receptor agonist [D-Ala2,N-Me-Phe4, Gly-ol]enkephalin (DAGO), and the selective mu-receptor antagonist (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), were determined in Swiss-Webster mice. A low dose of DAGO (0.92 micrograms/kg) moderately enhanced avoidance acquisition, whereas a 100 micrograms/kg dose of CTOP more dramatically impaired acquisition. However, the avoidance-enhancing dose of DAGO significantly increased locomotor activity as measured in a separate group of mice in the avoidance chamber, and the avoidance-impairing dose of CTOP significantly decreased activity. Under these same training conditions, earlier studies (Schulteis et al. 1988; Schulteis and Martinez 1990) demonstrated that enkephalins impaired avoidance learning, and selective delta-receptor antagonists such as ICI 174,864 enhanced learning; in contrast to the present study, both of these effects were dissociated from performance effects such as alterations in locomotor activity. Taken together, the results suggested that the effects of enkephalins were mediated by the delta-, but not mu-, class of opioid receptor.