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

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.

Authors+Show Affiliations

Department of Psychology, University of British Columbia, Vancouver, BC, Canada. ryanmc@psych.ubc.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22325231

Citation

McLaughlin, Ryan J., et al. "Prefrontal Cortical Anandamide Signaling Coordinates Coping Responses to Stress Through a Serotonergic Pathway." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 22, no. 9, 2012, pp. 664-71.
McLaughlin RJ, Hill MN, Bambico FR, et al. Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. Eur Neuropsychopharmacol. 2012;22(9):664-71.
McLaughlin, R. J., Hill, M. N., Bambico, F. R., Stuhr, K. L., Gobbi, G., Hillard, C. J., & Gorzalka, B. B. (2012). Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 22(9), 664-71. https://doi.org/10.1016/j.euroneuro.2012.01.004
McLaughlin RJ, et al. Prefrontal Cortical Anandamide Signaling Coordinates Coping Responses to Stress Through a Serotonergic Pathway. Eur Neuropsychopharmacol. 2012;22(9):664-71. PubMed PMID: 22325231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prefrontal cortical anandamide signaling coordinates coping responses to stress through a serotonergic pathway. AU - McLaughlin,Ryan J, AU - Hill,Matthew N, AU - Bambico,Francis R, AU - Stuhr,Kara L, AU - Gobbi,Gabriella, AU - Hillard,Cecilia J, AU - Gorzalka,Boris B, Y1 - 2012/02/10/ PY - 2011/08/04/received PY - 2011/11/08/revised PY - 2012/01/12/accepted PY - 2012/2/14/entrez PY - 2012/2/14/pubmed PY - 2013/1/18/medline SP - 664 EP - 71 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 22 IS - 9 N2 - 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. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/22325231/Prefrontal_cortical_anandamide_signaling_coordinates_coping_responses_to_stress_through_a_serotonergic_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(12)00021-1 DB - PRIME DP - Unbound Medicine ER -