title: Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine.
abstract: Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. In view of these observations, the goal of the current study was to determine the effects of repeated restraint stress (RRS) on the dendritic architecture of pyramidal neurons in the rat basolateral nucleus of the amygdala (CBL), as well as glutamate efflux in the CBL and central nucleus of the amygdala (CMX) via in vivo microdialysis. We also examined the ability of the antidepressant agomelatine to prevent RRS-induced neuroplasticity deficits. Compared with control rats, rats subjected to RRS exhibited atrophy of CBL pyramidal neurons, including decreases in total dendritic length, branch points, and dendritic complexity index. In addition, glutamate efflux was significantly reduced in the CMX of rats subjected to RRS, thereby identifying a potential neurochemical consequence of stress-induced dendritic atrophy of CBL pyramidal neurons. Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: C A
authors.initials: CA
authors.lastname: Grillo
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: M
authors.initials: M
authors.lastname: Risher
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: V A
authors.initials: VA
authors.lastname: Macht
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: A L
authors.initials: AL
authors.lastname: Bumgardner
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: A
authors.initials: A
authors.lastname: Hang
authors.affiliation: Neuropsychiatry Division, Institut de Recherches Internationales Servier, 6, Place des Pléiades, Courbevoie CEDEX, France.
authors.forename: C
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Neuropsychiatry Division, Institut de Recherches Internationales Servier, 6, Place des Pléiades, Courbevoie CEDEX, France.
authors.forename: E
authors.initials: E
authors.lastname: Mocaër
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: G G
authors.initials: GG
authors.lastname: Piroli
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States.
authors.forename: J R
authors.initials: JR
authors.lastname: Fadel
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, United States. Electronic address: lawrence.reagan@uscmed.sc.edu.
authors.forename: L P
authors.initials: LP
authors.lastname: Reagan
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001284:Atrophy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003345:Corticosterone / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D003345:Corticosterone; D018698:Glutamic Acid; C084711:agomelatine; D009281:Naphthalenes
keywords: basolateral amygdala; corticosterone; dendritic complexity index; depressive illness; in vivo microdialysis