Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice
| Autor: | Rifat J. Hussain, Lauren Jacobson |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Hypothalamo-Hypophyseal System Imipramine Cre recombinase Pituitary-Adrenal System Prefrontal Cortex Experimental and Cognitive Psychology Mice Transgenic Motor Activity Article Green fluorescent protein Behavioral Neuroscience chemistry.chemical_compound Glucocorticoid receptor Receptors Glucocorticoid Corticosterone Internal medicine medicine Animals Prefrontal cortex Anterior cingulate cortex Swimming Depressive Disorder Chemistry Immunohistochemistry Antidepressive Agents Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology nervous system Gene Knockdown Techniques Antidepressant Stress Psychological medicine.drug |
| Zdroj: | Physiologybehavior. 138 |
| ISSN: | 1873-507X |
| Popis: | Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. |
| Databáze: | OpenAIRE |
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