Effects of mu and delta opioid receptor agonists and antagonists on absence epilepsy in WAG/Rij rats.

The effects of various types of opioid receptor agonists and antagonists were determined in a genetic rat model for generalized absence epilepsy. Rats of the WAG/Rij strain spontaneously showed several hundred spike-wave discharges per day. Intracerebroventricular (i.c.v.) injections of the selective mu agonist DAMGO (0.2, 0.7 microgram) resulted in a dose-related increase in the number of spike-wave discharges, while the selective delta agonist DPDPE (20, 60 micrograms) was without effect. DAMGO reduced the duration of automatic behavior, enhanced the immobile behavior (after the low dose) and had no effect on exploratory behavior. On the other hand, DPDPE significantly enhanced the total time spent on exploration, but did not influence other behavioral parameters. There was no correlation between the ability to the drug to modulate the epileptic activity and behavioral changes. The nonselective antagonist naloxone, administered either i.p. (0.4, 2.0, 10 mg/kg) or i.c.v. (10, 50 micrograms), increased the number of spike-wave discharges in a dose-dependent way. The specific delta receptor antagonist naltrindole (0.3, 1 mg/kg) was without effect, as was the irreversible mu receptor antagonist beta-funaltrexamine (beta-FNA). Pretreatment with beta-FNA diminished the action of DAMGO. These results clearly indicate that activation of the mu opioid receptor increases the number of spike-wave discharges, and that modulation of delta receptors is not effective. On the other hand, the naloxone-induced enhancement of spike-wave discharges, suggests a tonic control of the epileptic activity by another opioid system. These results point to an important role of the mu-, but not delta-, receptor in facilitation of the epileptic activity in WAG/Rij rats.