title: Role of hypothalamic cannabinoid receptors in post-stroke depression in rats.
abstract: One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated. Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats. To this end, rats were treated with middle cerebral artery occlusion (MCAO) followed by chronic unpredictable mild stress (CUMS) treatment procedure. We then assessed the expression of CB1 and CB2 receptors in the hypothalamus, and evaluated the effects of pharmacological stimulations of CB1 or CB2 receptors on the expression and development of depression-like behaviors in PSD rats. We found that PSD rats exhibited decreased the expression of CB1 receptor, but not CB2 receptor, in the ventral medial hypothalamus (VMH). Such an effect was not observed in the dorsally adjacent brain regions. Furthermore, intra-VMH injections of CB2 receptor agonist, but not CB1 receptor agonist, attenuated the expression of depression-like behaviors in PSD rats. Finally, repeated intraperitoneal injections of CB1 or CB2 receptor agonists during CUMS treatment inhibited the development of depression-like behaviors in PSD rats. Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders.
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China. Electronic address: sshawang@sina.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China.
authors.forename: Jinqun
authors.initials: J
authors.lastname: Guan
authors.affiliation: Geriatric Neurology Department of Nanlou Clinical Division, PLA General Hospital, Fuxing Road 28, Beijing 100853, China. Electronic address: jjianjia@sina.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jia
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use; D002186:Cannabinoids / Q000627:therapeutic use; D003863:Depression / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D020521:Stroke / Q000150:complications / Q000473:pathology*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; C119325:arachidonyl-2-chloroethylamide; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
keywords: Cannabinoid receptor; Chronic unpredictable mild stress; Hypothalamus; Middle cerebral artery occlusion; Post-stroke depression