Faculty Collaboration Database

Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. Eur Neuropsychopharmacol 2012 Sep;22(9):664-71

Date

02/14/2012

Pubmed ID

22325231

Pubmed Central ID

PMC3366159

DOI

10.1016/j.euroneuro.2012.01.004

Scopus ID

2-s2.0-84865033949 (requires institutional sign-in at Scopus site)   87 Citations

Abstract

The endocannabinoid system has recently emerged as a vital component of the stress response and is an appealing target for the treatment of mood and anxiety disorders. Additionally, corticolimbic endocannabinoid signaling is important for stress-induced regulation of emotional behavior. However, the mechanism by which this occurs remains elusive. Combining biochemical and behavioral analyses within the forced swim test, we examined whether stress-induced regulation of endocannabinoid signaling in the medial prefrontal cortex contributes to behavioral responses to stress, and whether these responses are dependent on serotonergic neurotransmission. Forced swim stress produced a rapid and pronounced reduction in medial prefrontal anandamide content, but had no effect on 2-arachidonoylglycerol content within this region. Local administration of the anandamide hydrolysis inhibitor URB597 (0.01μg) into the ventromedial region of the prefrontal cortex decreased passive coping responses and increased active behavioral strategies, a phenomenon which was blocked by local antagonism of the CB(1) receptor. Furthermore, local inhibition of anandamide hydrolysis within the medial PFC increased the firing rate of serotonergic neurons within the dorsal raphe, suggesting that prefrontal cortical endocannabinoid signaling may modulate stress coping behaviors through a regulation of serotonergic neurotransmission. Accordingly, serotonin depletion prevented the ability of inhibition of anandamide hydrolysis within the medial PFC to promote active stress coping responses. Collectively, these data argue that stress-induced changes in endocannabinoid signaling within the medial PFC modulate stress-coping behaviors through a regulation of serotonergic neurotransmission and provide a neuroanatomical framework by which we may understand the mechanisms subserving the antidepressant potential of the endocannabinoid system.

Author List

McLaughlin RJ, Hill MN, Bambico FR, Stuhr KL, Gobbi G, Hillard CJ, Gorzalka BB

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Adaptation, Psychological
Animals
Arachidonic Acids
Benzamides
Cannabinoid Receptor Antagonists
Carbamates
Endocannabinoids
Enzyme Inhibitors
Fenclonine
Glycerides
Male
Microinjections
Piperidines
Polyunsaturated Alkamides
Prefrontal Cortex
Pyrazoles
Raphe Nuclei
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Serotonergic Neurons
Signal Transduction
Stress, Psychological