Upregulation of CB₁ receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure. Behav Brain Res 2013 Jan 15;237:333-7
Date
10/11/2012Pubmed ID
23047058Pubmed Central ID
PMC3501995DOI
10.1016/j.bbr.2012.09.053Scopus ID
2-s2.0-84867615880 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.
Author List
McLaughlin RJ, Hill MN, Dang SS, Wainwright SR, Galea LA, Hillard CJ, Gorzalka BBAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptation, PsychologicalAnalgesics
Animals
Cues
Cyclohexanols
Disease Models, Animal
Male
Prefrontal Cortex
Protein Binding
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Stress, Psychological
Swimming
Tritium
Up-Regulation
