ANATOMICAL AND FUNCTIONAL-ASPECTS OF MU-OPIOID RECEPTORS IN EPILEPTICWAG RIJ RATS/

Involvement of opioid systems in the pathogenesis of absence epilepsy has been postulated. However, the role of the mu opioid receptor has n ot been fully elucidated as yet. In the present study the role of this receptor in absence epilepsy was investigated autoradiographically an d pharmacologically. The density of mu opioid receptors in discrete br ain areas was quantified in WAG/Rij rats, which are regarded as a gene tic model of primarily generalized absence epilepsy and in three contr ol groups of non-epileptic rats. The autoradiographic study showed an abundance of mu opioid receptors (labelled with [H-3]DAMGO) in the str uctures involved in generation and propagation of spike-wave discharge s, such as the thalamus, cortex and striatum. A significant decrease i n the mu receptor density was found only in the frontal cortex of epil eptic WAG/Rij rats. In the pharmacological study, the effect of mu opi oid receptor activation in different brain structures of WAG/Rij raw o n the number of complexes of spike-wave discharges was investigated. D AMGO (0.02 and 0.07 mu g/0.5 mu l) was bilaterally injected into the t halamus, striatum and frontal cortex. DAMGO resulted in a dose-related increase in the number of spike-wave discharges after intracortical a nd intrastriatal administration by approximate to 200-300% and after i ntrathalamic administration by approximate to 500%. The injection of D AMGO into those structures had no significant effect of any kind on th e behavior measured,except for passive behavior which was reduced afte r intrastriatal injection. The high density of mu opioid receptors in the areas involved in the genesis of spike-wave discharges, as well as the highest responsiveness of thalamic mu opioid receptors to the epi leptogenic effects of DAMGO, suggest involvement of mu receptors in th e genesis of spike-wave discharges. (C) 1998 Elsevier Science B.V.