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 form, is associated with bursts of bilateral synchronous spike wave discharges (SWDs) recorded in the EEG. In a previous study, it was suggested that two features of the apomorphine-susceptible (APO-SUS) rat genotype, a relatively low dopaminergic reactivity of the nigrostriatal system and relatively high dopaminergic reactivity of the mesolimbic system, contribute to the high incidence of SWDs. Indeed, apomorphine-unsusceptible (APO-UNSUS) rats, characterized by opposite dopaminergic features, show considerably less SWDs 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 registered for a 19 hour period. Assuming that haloperidol decreases dopaminergic transmission in the nigrostriatal system via inhibition of the dopamine receptors and enhances dopaminergic transmission in the mesolimbic system via inhibition of the noradrenergic receptors, it was postulated that haloperidol would enhance the difference in dopaminergic reactivity between both systems in favor of the accumbens. Therefore, the second purpose in the present study was to investigate whether haloperidol (2 mg/kg, IP) could further potentiate SWD incidence when injected in the APO-SUS rats, already characterized by a relatively low dopaminergic reactivity of the nigrostriatal system and relatively high dopaminergic reactivity of the mesolimbic system, in comparison to the APO-UNSUS rat genotype. Finally, the third aim was to study if another epileptic rat genotype, the WAG/Rij, would show similar increases in SWD incidence following an injection with haloperidol as expected for the APO-SUS. First, previous findings were replicated: the value of the hourly number of SWDs decreased in the following order: APO-SUS > WAG/Rij > APO-UNSUS and ACI. Secondly, earlier data were extended by the fact 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. The 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 difference between the dopaminergic reactivity in the nigrostriatal and mesolimbic system. Finally, further research is required to provide evidence in favor of the hypothesis that the relative dominance of the dopaminergic mesolimbic system is smaller in WAG/Rij than in APO-SUS.
de Bruin
N M
NM
NICI/Department of Psychoneuropharmacology, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. debruin@nici.kun.nl
van Luijtelaar
E L
EL
Jansen
S J
SJ
Cools
A R
AR
Ellenbroek
B A
BA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology*; D005838:Genotype; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D017440:Photoperiod; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D011930:Reaction Time; D013378:Substantia Nigra / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D014677:Pharmaceutical Vehicles; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine