Striatal Patchwork of D1-like and D2-like Receptors Binding Densities in Rats with Genetic Audiogenic and Absence Epilepsies.

Binding densities to dopamine D1-like and D2-like receptors (D1DR and D2DR) were studied in brain regions of animals with genetic generalized audiogenic (AGS) and/or absence (AbS) epilepsy (KM, WAG/Rij-AGS, and WAG/Rij rats, respectively) as compared to non-epileptic Wistar (WS) rats. Convulsive epilepsy (AGS) exerted a major effect on the striatal subregional binding densities for D1DR and D2DR. An increased binding density to D1DR was found in the dorsal striatal subregions of AGS-prone rats. Similar changes were seen for D2DR in the central and dorsal striatal territories. Subregions of the nucleus accumbens demonstrated consistent subregional decreases in the binding densities of D1DR and D2DR in epileptic animals, irrespective of epilepsy types. This was seen for D1DR in the dorsal core, dorsal, and ventrolateral shell; and for D2DR in the dorsal, dorsolateral, and ventrolateral shell. An increased density of D2DR was found in the motor cortex of AGS-prone rats. An AGS-related increase in binding densities to D1DR and D2DR in the dorsal striatum and motor cortex, areas responsible for motor activity, possibly reflects the activation of brain anticonvulsive loops. General epilepsy-related decreases in binding densities to D1DR and D2DR in the accumbal subregions might contribute to behavioral comorbidities of epilepsy.

The prefrontal cortex shows widespread decrease in H3 histamine receptor binding densities in rats with genetic generalized epilepsies.

Distributions of brain H3 histamine receptors in regions of the prefrontal cortex were studied by assessing regional binding densities for [3 H](R)α-methylhistamine in coronal brain slices of normal rats and rats with genetically determined absence and/or audiogenic epilepsies. The three groups of epileptic rats displayed widespread significant decreases in H3 histamine receptor binding densities. A 20-25% decline was seen in the rostral aspects of the lateral prefrontal cortex, namely the granular, dysgranular, and dorsal agranular insular regions. The reduction was not specific for the epilepsy types. The same was observed in the rostral part of the primary cingulate cortex and the secondary midcingulate cortex. On borders of this core effect, several seizure-type specific declines were seen. Namely, the infralimbic, prelimbic and posterior agranular insular cortices demonstrated absence-epilepsy related reductions in the H3 histamine receptor binding densities. A decrease related to audiogenic seizures was noted in the rostral part of the piriform cortex. The pattern of widespread and seizure-type unspecific decline in H3 histamine receptor binding densities points to a common part of brain loops underlying generalized convulsive and non-convulsive types of epilepsy. It also might hint at putative seizure-related changes in the release of histamine from specific fibers innervating the prefrontal area.

H1 histamine receptor densities are increased in brain regions of rats with genetically generalized epilepsies.

Genetic animal models for convulsive, non-convulsive and mixed types of generalized epilepsies were used to establish putative histaminergic brain sites involved in the control of different types of epilepsy. Age matched rats of the KM strain (audiogenic seizures, AGS), WAG/Rij strain (absence seizures) and the WAG/Rij-AGS substrain (mixed model) were compared with a control group of Wistar rats on regional binding densities of H1 histamine receptors. Coronal slices of adult brains of the four groups were labeled with 3H pyrilamine, an antagonist of H1 histamine receptor and density of receptors was quantified with image analyses. All three groups of epileptic rats showed an increase in the density of H1 histamine receptor binding in the frontal motor cortex and interposed nucleus of cerebellum compared to the non-epileptic control group. Audiogenic epilepsy was characterized by increased H1 histamine receptor density in the frontal cortical and hippocampal regions, and in two midbrain (interpedunculus and lateral vestibular) nuclei. Absence epilepsy was characterized by a decrease in substantia nigra pars compacta, while the mixed model showed an elevation of H1 histamine receptor binding density in limbic regions such as the shell of the nucleus accumbens and the ventral tegmental area. It can be concluded that common changes in H1 histamine receptors can be found in genetic epilepsy models irrespective of the seizure type, and that each type of generalized epilepsy has its own pattern of H1 histamine receptor changes. It is speculated that H1 histamine receptors play a role in the brain's endogenous epilepsy control system.