Brain D2-Like Dopamine Receptor Distribution in Rats with Different Types of Genetic Epilepsy.

The distribution of the D2-like dopamine receptor (D2DR) in the cortex and striatum was compared between rats with absence, audiogenic, or combined genetically determined epilepsy and normal Wistar rats by autoradiography. A significantly lower D2DR binding density was observed in the dorsal and ventrolateral aspects of the nucleus accumbens in epileptic vs. non-epileptic rats. Rats with audiogenic epilepsy additionally showed a higher D2DR density in the dorsal striatum and motor and somatosensory cortex and a lower D2DR density in the ventrolateral part of the nucleus accumbens. The findings indicated that a common neuronal circuit is involved in the pathogenesis of both convulsive and nonconvulsive forms of generalized epilepsy.

Reduced H3 histamine receptor binding densities in the upper layers of motor cortex in rats prone to audiogenic convulsive seizures.

Fits of audiogenic seizures in rodents are considered as a model for generalized convulsive epilepsies in humans. The laminar distribution of the H3 histamine receptor binding densities was quantified in the motor cortex of two strains of rats with genetically determined generalized epilepsies, namely KM rats with audiogenic seizures only, and WAGRij rats with both audiogenic seizures and absence seizures. It was found that H3 histamine receptor binding densities in layer 2/3d of the primary and secondary motor cortices of the rats that experienced audiogenic seizure fits were significantly lower than in the cortices of control rats. Possible explanations are discussed.

Compensatory Changes in the Brain Dopaminergic System of WAG/Rij Rats Genetically Predisposed to Absence Epilepsy.

Involvement of the brain dopaminergic system in the age-related dynamics of absence epilepsy in WAG/Rij rats was examined by histological, immunohistochemical, and electrophysiological (EEG) methods. We revealed reduced expression of dopamine receptors in various brain structures prior to first manifestations of the disease (at the age of 1-3 months), reduced density of neurons in the center of nigrostriatal system (substantia nigra pars compacta) in 10-month-old rats in comparison with 1-month-old rats, and positive correlation between neural density in the substantia nigra and intensity of epileptic activity in EEG. It is hypothesized that loss of dopaminergic neurons and reduced nigrostriatal dopaminergic innervation of the brain could prevent the development of absence epilepsy in WAG/Rij rats.

[Age-related changes in behavior, in monoamines and their metabolites content, and in density of D1 and D2 dopamine receptors in the brain structures of WAG/Rij rats with depression-like pathology].

Behavior in the light-dark choice, open field, sucrose consumption/preference and forced swimming tests, monoamines and their metabolites content in 5 brain structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus, hippocampus), and density of D1- and D2-like dopamine receptors in the prefrontal cortex, nucleus accumbens and ventral tegmental area were studied in WAG/Rij rats at age of 36 days, 3 and 6 months. It has been found that with age, as far as spike-wave discharges aggravate, behavioral symptoms of depression (enhanced immobility in the forced swimming test, reduced sucrose consumption/preference) as well as a hypo-function of the mesolimbic dopaminergic brain system increase in WAG/Rij rats. At age of 36 days, when phenotypic expression of absence epilepsy in WAG/Rij rats is absent, neurochemical alterations in the brain suggesting a hypo-function of the mesolimbic dopaminergic system (deficit of dopamine in the nucleus accumbens), as well as symptoms of depression-like behavior, are not detected. In WAG/Rij rats, as well as in control rats, density of D1-like dopamine receptors in the nucleus accumbens decreased with age. A tendency to a lower density of D1-like dopamine receptors was found in WAG/Rij rats compared with controls at age of 3 months. In contrast with control rats, in WAG/Rij rats, density of D2-like dopamine receptors in the nucleus accumbens increased with age. Higher density of D2-like dopamine receptors was observed in WAG/Rij rats compared with controls only at age of 6 months when a hypo-function of the mesolimbic dopaminergic bran system was extremely pronounced indicating that this increase is a compensatory response to a deficit of dopamine.

Distribution of D1-like and D2-like dopamine receptors in the brain of genetic epileptic WAG/Rij rats.

The densities of the dopamine (DA) D1-like and D2-like receptors were studied by autoradiography in brain regions of rats with (WAG/Rij strain) and without (ACI strain) genetic absence epilepsy. The core of the nucleus accumbens in WAG/Rij rats had a lower density of D1-like receptors than in ACI rats, a reduction of both D1-like and D2-like DA receptors was also found for the dorsal striatum (dorsal caudate-putamen). On the other hand, the density of D2-like receptors was higher in cortical (frontal and parietal) regions and lower in the CA3 region of the hippocampus of WAG/Rij, as compared to ACI rats. These results give new information about possible malfunction of the brain dopaminergic system in the WAG/Rij rat model of absence epilepsy. It seems that there are differences between WAG/Rij and other models of absence epilepsy, especially concerning the role of striatum.