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GABAergic and endocannabinoid dysfunction in anxiety - future therapeutic targets?
Curr Pharm Des. 2008; 14(33):3508-17.CP

Abstract

With a lifetime prevalence of up to 25% anxiety disorders are among the most frequently occurring psychiatric disorders. The etiology of anxiety is considered to be multifactorial with an interaction of neurobiological, psychological and environmental factors. With regard to neurobiological factors, several neurochemical systems and neuroanatomical circuits have been discussed to be involved. In particular, anxiety might be a result of insufficient inhibitory control, pointing towards a major role of the gamma-amino-butyric acid (GABA) system in these disorders. Preclinical and clinical studies discuss a decreased GABAergic inhibition in anxiety and patients with anxiety disorders. In view of these findings it is intriguing that benzodiazepines, which currently represent the most potent and powerful anxiolytic agents, act through an enhancement of GABAergic inhibition targeting the GABAA receptor. Thus, it has been suggested that the GABAergic system might represent a promising future target for new pharmacologic strategies for the treatment of anxiety. Closely linked to the GABAergic system is the endocannabinoid system, which might also play an important role in this group of disorders. The endocannabinoid system has particularly been involved in extinction learning, suggesting a key role of this system in the process of fear extinction. In this paper, both the GABAergic and the endocannabinoid system will be reviewed with regard to their role in anxiety and anxiety disorders in humans with particular attention to findings from genetic and neuroimaging studies. Moreover, both systems will be discussed as potential therapeutic targets.

Authors+Show Affiliations

Department of Psychiatry, University of Münster, Münster, Germany.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19075727

Citation

Domschke, K, and P Zwanzger. "GABAergic and Endocannabinoid Dysfunction in Anxiety - Future Therapeutic Targets?" Current Pharmaceutical Design, vol. 14, no. 33, 2008, pp. 3508-17.
Domschke K, Zwanzger P. GABAergic and endocannabinoid dysfunction in anxiety - future therapeutic targets? Curr Pharm Des. 2008;14(33):3508-17.
Domschke, K., & Zwanzger, P. (2008). GABAergic and endocannabinoid dysfunction in anxiety - future therapeutic targets? Current Pharmaceutical Design, 14(33), 3508-17.
Domschke K, Zwanzger P. GABAergic and Endocannabinoid Dysfunction in Anxiety - Future Therapeutic Targets. Curr Pharm Des. 2008;14(33):3508-17. PubMed PMID: 19075727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABAergic and endocannabinoid dysfunction in anxiety - future therapeutic targets? AU - Domschke,K, AU - Zwanzger,P, PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/2/13/medline SP - 3508 EP - 17 JF - Current pharmaceutical design JO - Curr. Pharm. Des. VL - 14 IS - 33 N2 - With a lifetime prevalence of up to 25% anxiety disorders are among the most frequently occurring psychiatric disorders. The etiology of anxiety is considered to be multifactorial with an interaction of neurobiological, psychological and environmental factors. With regard to neurobiological factors, several neurochemical systems and neuroanatomical circuits have been discussed to be involved. In particular, anxiety might be a result of insufficient inhibitory control, pointing towards a major role of the gamma-amino-butyric acid (GABA) system in these disorders. Preclinical and clinical studies discuss a decreased GABAergic inhibition in anxiety and patients with anxiety disorders. In view of these findings it is intriguing that benzodiazepines, which currently represent the most potent and powerful anxiolytic agents, act through an enhancement of GABAergic inhibition targeting the GABAA receptor. Thus, it has been suggested that the GABAergic system might represent a promising future target for new pharmacologic strategies for the treatment of anxiety. Closely linked to the GABAergic system is the endocannabinoid system, which might also play an important role in this group of disorders. The endocannabinoid system has particularly been involved in extinction learning, suggesting a key role of this system in the process of fear extinction. In this paper, both the GABAergic and the endocannabinoid system will be reviewed with regard to their role in anxiety and anxiety disorders in humans with particular attention to findings from genetic and neuroimaging studies. Moreover, both systems will be discussed as potential therapeutic targets. SN - 1873-4286 UR - https://www.unboundmedicine.com/medline/citation/19075727/GABAergic_and_endocannabinoid_dysfunction_in_anxiety___future_therapeutic_targets L2 - http://www.eurekaselect.com/68184/article DB - PRIME DP - Unbound Medicine ER -