Abstract
Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. We investigated the role of α2 adrenoceptors in a neonatal domoic acid (DOM) rat model of epilepsy.
Male Sprague-Dawley rats (n=6-7 per group) were injected (s.c.) daily from postnatal day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist and scanned in a micro positron emission tomography (PET) scanner.
DOM60 spent more time in the periphery during the open field test and less time struggling in the forced swim test compared to the saline treated rats. microPET data revealed that DOM60 rats had a 40-47 % reduction in [11C]yohimbine binding in limbic and cortical brain regions relative to saline treated rats.
We conclude that neonatal administration of DOM combined with the potential stress associated with behavioural testing results in a significant decrease in [11C]yohimbine binding in limbic and cortical brain regions. We suggest that the observed downregulation of α2 adrenoceptors is a result of elevated extracellular noradrenaline which may represent a form of preconditioning to decrease seizure susceptibility of the brain.
Male Sprague-Dawley rats (n=6-7 per group) were injected (s.c.) daily from postnatal day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist and scanned in a micro positron emission tomography (PET) scanner.
DOM60 spent more time in the periphery during the open field test and less time struggling in the forced swim test compared to the saline treated rats. microPET data revealed that DOM60 rats had a 40-47 % reduction in [11C]yohimbine binding in limbic and cortical brain regions relative to saline treated rats.
We conclude that neonatal administration of DOM combined with the potential stress associated with behavioural testing results in a significant decrease in [11C]yohimbine binding in limbic and cortical brain regions. We suggest that the observed downregulation of α2 adrenoceptors is a result of elevated extracellular noradrenaline which may represent a form of preconditioning to decrease seizure susceptibility of the brain.
| Originalsprog | Engelsk |
|---|---|
| Publikationsdato | jul. 2015 |
| Status | Udgivet - jul. 2015 |
| Begivenhed | NeuroConX - Charlottetown, Prince Edward Island, Canada Varighed: 12 jul. 2015 → 14 jul. 2015 |
Konference
| Konference | NeuroConX |
|---|---|
| Land/Område | Canada |
| By | Charlottetown, Prince Edward Island |
| Periode | 12/07/2015 → 14/07/2015 |