Neonatal Domoic Acid Alters in Vivo Binding of [C]yohimbine to α-adrenoceptors in Adult Rat Brain

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2016 Aug 26

PMID 27557950

Citations 4

Authors

Majken B Thomsen

Thea P Lillethorup

Steen Jakobsen

Erik H Nielsen

Mette Simonsen

Gregers Wegener

Anne M Landau

R Andrew Tasker

Affiliations

Soon will be listed here.

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.

Citing Articles

Life Course Considerations in Environmental Health: Developmental Neurotoxicity of Domoic Acid at Doses Below Acute Effect Levels in Adult Humans.

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Public health risks associated with chronic, low-level domoic acid exposure: A review of the evidence.

Petroff R, Hendrix A, Shum S, Grant K, Lefebvre K, Burbacher T Pharmacol Ther. 2021; 227:107865.

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In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET.

Thomsen M, Jacobsen J, Lillethorup T, Schacht A, Simonsen M, Romero-Ramos M J Cereb Blood Flow Metab. 2020; 41(4):819-830.

PMID: 32538280 PMC: 7983510. DOI: 10.1177/0271678X20931140.

Radioligand binding analysis of α adrenoceptors with [C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding.

Phan J, Landau A, Jakobsen S, Wong D, Gjedde A Sci Rep. 2017; 7(1):15979.

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