Increased
dopaminergic tone in Genetic Absence Epilepsy
Rats from Strasbourg (GAERS): evidence from
quinpirole-induced yawning and microdialysis
experiments
Colin DERANSART, Hélène
BERNARD, Anne BERTRAND*, Marc SAVASTA*, Antoine
DEPAULIS
Institution Grenoble -
Institut des Neurosciences Centre de recherche
Inserm U 836-UJF-CEA-CHU Equipe 9: Dynamique des
Réseaux Synchrones Epileptiques
*Equipe 10: Dynamique
des Réseaux Neuronaux du Mouvement
Université Joseph Fourier -
Faculté de Médecine Domaine de la
Merci 38700 La Tronche
Purpose : In rats with absence
epilepsy (GAERS), systemic and intrastriatal
dopamimetics suppress seizures, whereas
antagonists aggravate them. In addition, D3
receptor transcripts are overexpressed in the
nucleus accumbens core (NacC) as compared to
inbred non epileptic control rats (NEC). The
hypothesis of an increased dopaminergic tone in
GAERS was thus addressed using pharmacology and
microdialysis.
Method: In GAERS and NEC (i)
spontaneous and quinpirole-induced yawning
behaviour and (ii) changes in intra-accumbens
dopamine contents induced by amphetamine and K
and measured by microdialysis were investigated.
Results: Spontaneous yawning was significantly
decreased in GAERS (0.3±0.2 yawn/hr, n=9)
as compared to NEC (5.4±1.2, n=8) and
Wistar Harlan rats (9.7±2.3, n=7).
Quinpirole-induced yawning was significantly
increased in GAERS (29.4±4.9) as compared
to NEC (10.5±2.7) and Wistar-Harlan rats
(22.6±3.5). Quinpirole also increased the
number of absence-seizures in GAERS
(+47.4±8.6%). When compared to NEC, basal
levels of DA were 40% lower in GAERS whereas
amphetamine and K produced a higher increase in
extracellular dopamine in GAERS.
Conclusion : The increased
quinpirole-induced yawning in GAERS may account
for an overexpression in D3 transcripts. The
increased responsiveness of dopamine
transmission observed in GAERS after
pharmacological manipulations, as compared to
NEC, suggests a « hyperdopaminergic »
phenotype of GAERS. Altogether, these data
support that GAERS have an impaired DA tone that
may be associated with the development of
mechanisms controlling absences seizures
