Julie Gardener
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Deficiency in Endocannabinoid Signaling in the Nucleus Accumbens Induced by Chronic Unpredictable Stress
Wei Wang1,3, Dalong Sun1,2,3, Bin Pan1, Christopher J Roberts1, Xinglai Sun1, Cecilia J Hillard1 and Qing-song Liu1
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
2Department of Geriatrics, Shandong University, Qilu Hospital, Jinan, People's Republic of China
Correspondence: Dr Qing-song Liu, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1-414-456-8877; Fax: +1-414-456-6545; E-mail: qsliu@mcw.edu
3These authors contributed equally to this work.
Received 28 April 2010; Accepted 16 June 2010; Published online 21 July 2010.
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Abstract
The nucleus accumbens (NAc) is a critical component of the reward circuitry, and dysfunction of the NAc may account for anhedonia and other symptoms of depression. Here, we investigated whether alterations in endocannabinoid (eCB) signaling in the NAc contribute to depression-like behaviors induced by chronic unpredictable stress (CUS) in mice. We compared three types of eCB/CB1 receptor-mediated synaptic plasticity in slices prepared from the NAc core of control and stress-exposed mice: depolarization-induced suppression of excitation, long-term depression, and the depression of field excitatory postsynaptic potentials (fEPSPs) induced by group I metabotropic glutamate receptor agonist DHPG. CUS (5—6-week exposure to stressors), but not sub-CUS (1 week exposure to stressors), induces depression-like behaviors and impairs these forms of eCB/CB1 receptor-mediated plasticity examined in the NAc core. Neither sub-CUS nor CUS altered the tissue contents of the eCBs, anandamide and 2-arachidonoylglycerol in the striatum. However, exposure to CUS, but not to sub-CUS, attenuated the depression of fEPSPs induced by the CB1 receptor agonist WIN 55 212-2. CUS exposure reduced the maximal effect without affecting the EC50 of WIN 55 212-2 to induce fEPSP depression. Thus, impaired CB1 receptor function could account for CUS-induced deficiency in eCB signaling in the NAc. Both CUS-induced deficiency in eCB signaling and depression-like behaviors were reversed by in vivo administration of antidepressant fluoxetine. These results suggest that downregulation of eCB signaling in the NAc occurs after CUS and contributes to the pathophysiology of depression.
Keywords: chronic unpredictable stress; endocannabinoid; CB1 receptor; DSE; nucleus accumbens; depression
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Source: Neuropsychopharmacology - Abstract of article: Deficiency in Endocannabinoid Signaling in the Nucleus Accumbens Induced by Chronic Unpredictable Stress
Wei Wang1,3, Dalong Sun1,2,3, Bin Pan1, Christopher J Roberts1, Xinglai Sun1, Cecilia J Hillard1 and Qing-song Liu1
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA
2Department of Geriatrics, Shandong University, Qilu Hospital, Jinan, People's Republic of China
Correspondence: Dr Qing-song Liu, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1-414-456-8877; Fax: +1-414-456-6545; E-mail: qsliu@mcw.edu
3These authors contributed equally to this work.
Received 28 April 2010; Accepted 16 June 2010; Published online 21 July 2010.
Top of page
Abstract
The nucleus accumbens (NAc) is a critical component of the reward circuitry, and dysfunction of the NAc may account for anhedonia and other symptoms of depression. Here, we investigated whether alterations in endocannabinoid (eCB) signaling in the NAc contribute to depression-like behaviors induced by chronic unpredictable stress (CUS) in mice. We compared three types of eCB/CB1 receptor-mediated synaptic plasticity in slices prepared from the NAc core of control and stress-exposed mice: depolarization-induced suppression of excitation, long-term depression, and the depression of field excitatory postsynaptic potentials (fEPSPs) induced by group I metabotropic glutamate receptor agonist DHPG. CUS (5—6-week exposure to stressors), but not sub-CUS (1 week exposure to stressors), induces depression-like behaviors and impairs these forms of eCB/CB1 receptor-mediated plasticity examined in the NAc core. Neither sub-CUS nor CUS altered the tissue contents of the eCBs, anandamide and 2-arachidonoylglycerol in the striatum. However, exposure to CUS, but not to sub-CUS, attenuated the depression of fEPSPs induced by the CB1 receptor agonist WIN 55 212-2. CUS exposure reduced the maximal effect without affecting the EC50 of WIN 55 212-2 to induce fEPSP depression. Thus, impaired CB1 receptor function could account for CUS-induced deficiency in eCB signaling in the NAc. Both CUS-induced deficiency in eCB signaling and depression-like behaviors were reversed by in vivo administration of antidepressant fluoxetine. These results suggest that downregulation of eCB signaling in the NAc occurs after CUS and contributes to the pathophysiology of depression.
Keywords: chronic unpredictable stress; endocannabinoid; CB1 receptor; DSE; nucleus accumbens; depression
Top of page
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
RESEARCH
Vascular Endothelial Growth Factor Signaling is Required for the Behavioral Actions of Antidepressant Treatment: Pharmacological and Cellular Characterization
Neuropsychopharmacology Original Article
A single in-vivo exposure to Δ9THC blocks endocannabinoid-mediated synaptic plasticity
Nature Neuroscience Brief Communication (01 Jun 2004)
Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole
Molecular Psychiatry Original Article
The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors
Nature Neuroscience Article (01 Aug 2010)
Chronic Δ 9 -Tetrahydrocannabinol During Adolescence Provokes Sex-Dependent Changes in the Emotional Profile in Adult Rats: Behavioral and Biochemical Correlates
Neuropsychopharmacology Original Article
Source: Neuropsychopharmacology - Abstract of article: Deficiency in Endocannabinoid Signaling in the Nucleus Accumbens Induced by Chronic Unpredictable Stress
