Implantation of a slow release corticosterone pellet induces long-term alterations in serotonergic neurochemistry in the rat brain.
Many studies point to an involvement of deficits in the serotonergic nervous system and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis function with depression. Indeed early life stress, involving HPA axis activation, may predispose susceptible individuals to develop depression in later life. This study investigates the effects of elevating the neuroendocrine stress hormone, corticosterone, for 1 week in adolescent rats on markers of serotonergic neurone function at adulthood. Slow release corticosterone pellets were implanted for 7 days and various serotonergic parameters, as well as plasma corticosterone levels, were measured on day 7 or on day 28 (21 days following removal of the pellet). The corticosterone implant attenuated weight gain and reduced adrenal weights compared to that in control rats implanted with a cholesterol pellet. After 7 days, with the implant still in place, the diurnal variation in plasma corticosterone was reduced so that the level was approximately at that of the evening peak throughout the day. Twenty-one days after removal of the implant, the diurnal variation in plasma corticosterone returned. Corticosterone treatment decreased [3H] 8-hydroxy-2-(di-n-propylamino)tetralin binding to the 5-hydroxytryptamine1A receptor in the cortex but not in the hippocampus. Corticosterone treatment also enhanced the circadian rhythm observed in 5-hydroxyindoleacetic acid level and the ratio of 5-hydroxyindoleacetic acid to the 5-hydroxytryptamine in the frontal cortex. Despite corticosterone pellet removal 21 days earlier, there was a persistent decrease in whole body and adrenal weight, cortical 5-hydroxytryptamine1A receptor binding and an alteration in the diurnal variation in the 5-hydroxytryptamine "turnover" in the frontal cortex.
Bush
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University of Nottingham, Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Middlemiss
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Marsden
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Fone
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D000311:Adrenal Glands / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D003863:Depression / Q000503:physiopathology*; D004195:Disease Models, Animal; D004343:Drug Implants; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009929:Organ Size / Q000502:physiology; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D013995:Time
D002352:Carrier Proteins; D003345:Corticosterone; D004343:Drug Implants; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493232:Slc6a4 protein, rat