Opioids and spike-wave discharges in rats: Pharmacological studies

Numerous studies have provided evidence for the involvement of opioids in the mechanisms of various forms of epilepsy. Most have investigated the effects of opioids in the control and genesis of convulsive epilepsy, whereas data on opioids mechanisms with respect to nonconvulsive epilepsy are almost lacking. Therefore, we investigated the role of the opioid subsystems in WAG/Rij rats, a genetic rat model of human absence epilepsy. Six-month-old male WAG/Rij were chronically provided with EEG electrodes and some with cannulas in the lateral ventricle. The baseline EEG was measured, and the drugs or solvent was injected. The EEG was recorded for 1 h, and the number and duration of spike-wave discharges (SWD) was counted. SWD were facilitated by the nonspecific opioid antagonist naloxone (intraperitoneally), suggesting that SWD are tonically inhibited by the endogenous opioid system. Next, specific mu, delta and kappa agonists and antagonists were evaluated. The mu receptor agonist DAMGO increased (intracerebroventricularly, i.c.v.) markedly the number of SWD, whereas DPDPE, a delta receptor agonist, had no effect. Three kappa agonists (i.c.v. or subcutaneously) US0488H, U69593, or PDI 17301 dosedependently inhibited the number of SWD. These effects could be antagonized by the kappa antagonist Nor-BNI. Nor-BN1 itself enhanced the number of SWD, but the mu antagonist naltrindole had no effect. Endogenous opioids, which act through the kappa receptors, tonically control the initiation of SWD. Kappa agonists, if devoid of psychomimetic effects, might be useful antiabsence drugs