Anatomical and functional aspects of μ opioid receptors in epileptic WAG/Rij rats

Abstract 

Involvement of opioid systems in the pathogenesis of absence epilepsy has been postulated. However, the role of the μ opioid receptor has not been fully elucidated as yet. In the present study the role of this receptor in absence epilepsy was investigated autoradiographically and pharmacologically. The density of μ opioid receptors in discrete brain areas was quantified in WAG/Rij rats, which are regarded as a genetic model of primarily generalized absence epilepsy and in three control groups of non-epileptic rats. The autoradiographic study showed an abundance of μ opioid receptors (labelled with [³H]DAMGO) in the structures involved in generation and propagation of spike-wave discharges, such as the thalamus, cortex and striatum. A significant decrease in the μ receptor density was found only in the frontal cortex of epileptic WAG/Rij rats. In the pharmacological study, the effect of μ opioid receptor activation in different brain structures of WAG/Rij rats on the number of complexes of spike-wave discharges was investigated. DAMGO (0.02 and 0.07 μg/0.5 μl) was bilaterally injected into the thalamus, striatum and frontal cortex. DAMGO resulted in a dose-related increase in the number of spike-wave discharges after intracortical and intrastriatal administration by ≈200–300% and after intrathalamic administration by ≈500%. The injection of DAMGO into those structures had no significant effect of any kind on the behavior measured, except for passive behavior which was reduced after intrastriatal injection. The high density of μ opioid receptors in the areas involved in the genesis of spike-wave discharges, as well as the highest responsiveness of thalamic μ opioid receptors to the epileptogenic effects of DAMGO, suggest involvement of μ receptors in the genesis of spike-wave discharges.

Keywords:  Absence epilepsy, WAG/Rij rats, Spike-wave discharges, DAMGO, μ opioid receptor