Neonatal domoic acid alters in vivo binding of [C]yohimbine to α-adrenoceptors in adult rat brain.

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Title: Neonatal domoic acid alters in vivo binding of [C]yohimbine to α-adrenoceptors in adult rat brain.
Authors: Thomsen, Majken, Lillethorup, Thea, Jakobsen, Steen, Nielsen, Erik, Simonsen, Mette, Wegener, Gregers, Landau, Anne, Tasker, R.
Source: Psychopharmacology. Oct2016, Vol. 233 Issue 21/22, p3779-3785. 7p.
Subjects: Domoic acid, Yohimbine, Adrenergic receptors, Animal models in epilepsy research, Laboratory rats
Abstract: Rationale: Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. Objective: We investigated the role of α-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model of epilepsy. Methods: We injected male Sprague-Dawley rats daily from postnatal day 8-14 with saline or one of two sub-convulsive doses, 20 μg/kg (DOM20) or 60 μg/kg (DOM60) DOM, an AMPA/kainate receptor agonist. The rats were observed in open field, social interaction and forced swim tests at day 50, 75 and 98, respectively. At ~120 days of age, four rats per group were injected and scanned with [C]yohimbine, an α-adrenoceptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner to measure αadrenoceptor binding. Results: DOM60-treated rats spent more time in the periphery during the open field test and had a significant 26-33 % reduction in [C]yohimbine binding in the hypothalamus, hippocampus and orbital prefrontal cortex compared to saline-treated rats. On the other hand, DOM20 rats had a significant 34-40 % increase in [C]yohimbine binding in the hypothalamus, amygdala and entorhinal cortex compared to saline-treated rats, with no obvious behavioural differences. Conclusions: The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long-term changes in α-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
Description
Abstract:Rationale: Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. Objective: We investigated the role of α-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model of epilepsy. Methods: We injected male Sprague-Dawley rats daily from postnatal day 8-14 with saline or one of two sub-convulsive doses, 20 μg/kg (DOM20) or 60 μg/kg (DOM60) DOM, an AMPA/kainate receptor agonist. The rats were observed in open field, social interaction and forced swim tests at day 50, 75 and 98, respectively. At ~120 days of age, four rats per group were injected and scanned with [C]yohimbine, an α-adrenoceptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner to measure αadrenoceptor binding. Results: DOM60-treated rats spent more time in the periphery during the open field test and had a significant 26-33 % reduction in [C]yohimbine binding in the hypothalamus, hippocampus and orbital prefrontal cortex compared to saline-treated rats. On the other hand, DOM20 rats had a significant 34-40 % increase in [C]yohimbine binding in the hypothalamus, amygdala and entorhinal cortex compared to saline-treated rats, with no obvious behavioural differences. Conclusions: The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long-term changes in α-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype. [ABSTRACT FROM AUTHOR]
ISSN:00333158
DOI:10.1007/s00213-016-4416-5