title: Activation of beta- and alpha-2-adrenoceptors in the basolateral amygdala has opposing effects on hippocampal-prefrontal long-term potentiation.
abstract: Noradrenaline (NA), released by the locus coeruleus (LC), plays a key role in mediating the effects of stress on memory functions. The LC provides diffuse projections to many forebrain nuclei including the hippocampus, the prefrontal cortex (PFC), and the basolateral amygdala (BLA). These three structures are intricately interlinked. The hippocampal-prefrontal (H-PFC) pathway is involved in various cognitive functions. The first aim of this study was to examine the role of BLA in H-PFC plasticity by infusion of drugs to activate and inactivate the BLA and studying the effects on H-PFC long-term potentiation (LTP) in the rat in vivo. Activation of the BLA with glutamate impaired, while inactivation with muscimol augmented, H-PFC LTP. This study also aimed to demonstrate how directly applying noradrenaline and other noradrenergic agents in the BLA can affect H-PFC LTP. Noradrenaline at 1μg/0.2μl enhanced H-PFC LTP. Stimulating alpha-2-adrenoceptors in the BLA with clonidine enhanced LTP while blocking alpha-2 adrenoceptors with idazoxan impaired it. Propranolol, a non-selective beta antagonist, enhanced H-PFC LTP while isoprenaline, a non-selective beta agonist, decreased H-PFC LTP. These results suggest that the BLA regulates H-PFC plasticity negatively and also provide a mechanism by which noradrenaline in the BLA can affect H-PFC plasticity via alpha-2 and beta adrenoceptors.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Singapore Institute for Neurotechnology (SINAPSE), Singapore; INSERM, UMR_S 894, Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Ee Peng
authors.initials: EP
authors.lastname: Lim
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; Singapore Institute for Neurotechnology (SINAPSE), Singapore. Electronic address: gavindawe@nus.edu.sg.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
authors.affiliation: INSERM, UMR_S 894, Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Thérèse M
authors.initials: TM
authors.lastname: Jay
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D019329:Idazoxan / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan
keywords: Basolateral amygdala; Hippocampus; Long-term potentiation; Noradrenaline; Prefrontal cortex