Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress
Deficits in cognitive functioning and flexibility are seen following both chronic stress and modulation of endogenous cannabinoid (eCB) signaling. Here, we investigated whether alterations in eCB signaling might contribute to the cognitive impairments induced by chronic stress. Chronic stress impair...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2005-03, Vol.30 (3), p.508-515 |
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| creator | HILL, Matthew N PATEL, Sachin CARRIER, Erica J RADEMACHER, David J ORMEROD, Brandi K HILLARD, Cecilia J GORZALKA, Boris B |
| description | Deficits in cognitive functioning and flexibility are seen following both chronic stress and modulation of endogenous cannabinoid (eCB) signaling. Here, we investigated whether alterations in eCB signaling might contribute to the cognitive impairments induced by chronic stress. Chronic stress impaired reversal learning and induced perseveratory behavior in the Morris water maze without significant effect on task acquisition. These cognitive impairments were reversed by exogenous cannabinoid administration, suggesting deficient eCB signaling underlies these phenomena. In line with this hypothesis, chronic stress downregulated CB1 receptor expression and significantly reduced the content of the endocannabinoid 2-arachidonylglycerol within the hippocampus. CB1 receptor density and 2-arachidonylglycerol content were unaffected in the limbic forebrain. These data suggest that stress-induced downregulation of hippocampal eCB signaling contributes to problems in behavioral flexibility and could play a role in the development of perseveratory and ruminatory behaviors in stress-related neuropsychiatric disorders. |
| doi_str_mv | 10.1038/sj.npp.1300601 |
| format | Article |
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Here, we investigated whether alterations in eCB signaling might contribute to the cognitive impairments induced by chronic stress. Chronic stress impaired reversal learning and induced perseveratory behavior in the Morris water maze without significant effect on task acquisition. These cognitive impairments were reversed by exogenous cannabinoid administration, suggesting deficient eCB signaling underlies these phenomena. In line with this hypothesis, chronic stress downregulated CB1 receptor expression and significantly reduced the content of the endocannabinoid 2-arachidonylglycerol within the hippocampus. CB1 receptor density and 2-arachidonylglycerol content were unaffected in the limbic forebrain. These data suggest that stress-induced downregulation of hippocampal eCB signaling contributes to problems in behavioral flexibility and could play a role in the development of perseveratory and ruminatory behaviors in stress-related neuropsychiatric disorders.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/sj.npp.1300601</identifier><identifier>PMID: 15525997</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Animals ; Behavioral psychophysiology ; Biological and medical sciences ; Cannabinoid Receptor Modulators - metabolism ; Cannabinoids - pharmacology ; Copulation - drug effects ; Copulation - physiology ; Endocannabinoids ; Female ; Fundamental and applied biological sciences. 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Psychology</subject><subject>Hippocampus - physiopathology</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Maze Learning - physiology</subject><subject>Mental disorders</subject><subject>Neurotransmission and behavior</subject><subject>Physiology</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. 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| subjects | Animals Behavioral psychophysiology Biological and medical sciences Cannabinoid Receptor Modulators - metabolism Cannabinoids - pharmacology Copulation - drug effects Copulation - physiology Endocannabinoids Female Fundamental and applied biological sciences. Psychology Hippocampus - physiopathology Male Maze Learning - drug effects Maze Learning - physiology Mental disorders Neurotransmission and behavior Physiology Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Rats Rats, Long-Evans Receptor, Cannabinoid, CB1 - physiology Reference Values Signal Transduction - physiology Stress Stress, Psychological - blood Stress, Psychological - physiopathology Toxicology |
| title | Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress |
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