Dopamine characteristics in different rat genotypes: the relation to absence epilepsy

Dopaminergic neurotransmission has been shown to participate in the control of absence epilepsy. This type of epilepsy, a generalized non-convulsive f orm, is associated with bursts of bilateral synchronous spike wave discharg es (SWDs) recorded in the EEG. In a previous study, it was suggested that t wo features of the apomorphine-susceptible (APO-SUS) rat genotype, a relati vely low dopaminergic reactivity of the nigrostriatal system and relatively high dopaminergic reactivity of the mesolimbic system, contribute to the h igh incidence of SWDs. Indeed, apomorphine-unsusceptible (APO-UNSUS) rats, characterized by opposite dopaminergic features, show considerably less SWD s than APO-SUS rats. The first goal of the present study was to assess the baseline SWD incidence in four rat genotypes (WAG/Rij, ACI, APO-SUS and APO -UNSUS) in order to replicate previous findings. It was expected that both the APO-SUS and WAG/Rij rats would show a considerably higher SWD incidence in comparison to the APO-UNSUS and ACI rats. For this purpose, rats were r egistered for a 19 hour period. Assuming that haloperidol decreases dopamin ergic transmission in the nigrostriatal system via inhibition of the dopami ne receptors and enhances dopaminergic transmission in the mesolimbic syste m via inhibition of the noradrenergic receptors, it was postulated that hal operidol would enhance the difference in dopaminergic reactivity between bo th systems in favor of the accumbens. Therefore, the second purpose in the present study was to investigate whether haloperidol (2 mg/kg, IP) could fu rther potentiate SWD incidence when injected in the APO-SUS rats, already c haracterized by a relatively low dopaminergic reactivity of the nigrostriat al system and relatively high dopaminergic reactivity of the mesolimbic sys tem, in comparison to the APO-UNSUS rat genotype. Finally, the third aim wa s to study if another epileptic rat genotype, the WAG/Rij, would show simil ar increases in SWD incidence following an injection with haloperidol as ex pected for the APO-SUS. First, previous findings were replicated: the value of the hourly number of SWDs decreased in the following order: APO-SUS > W AG/Rij > APO-UNSUS and ACI. Secondly, earlier data were extended by the fac t that the APO-SUS responded to a systemic injection of haloperidol with an increase in SWD number and duration, in contrast to the APO-UNSUS rats. Th e hypothesis that the SWD incidence would be mostly affected by haloperidol in the APO-SUS rats, was confirmed by these findings. It is suggested that haloperidol increases the SWD incidence in APO-SUS rats by enhancing the d ifference between the dopaminergic reactivity in the nigrostriatal and meso limbic system. Finally, further research is required to provide evidence in favor of the hypothesis that the relative dominance of the dopaminergic me solimbic system is smaller in WAG/Rij than in APO-SUS. (C) 2000 Elsevier Sc ience Ireland Ltd and the Japan Neuroscience Society. All rights reserved.