New Findings on the Neurotransmitter Modulation of Defense in the Dorsal Periaqueductal Gray

Author(s): Frederico Guilherme Graeff, Ana Beatriz Sant'Ana, Heloisa Helena Vilela-Costa, Helio Zangrossi Jr..

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 14 , Issue 8 , 2015

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Abstract:

The dorsal periaqueductal gray (DPAG) has long been implicated in the pathophysiology of anxiety, particularly in panic disorder (PD). Evidence obtained with animal models indicates that different neurotransmitters/neuromodulators in this midbrain area are involved in the regulation of anxiety- (e.g. inhibitory avoidance) and panic- (e.g. escape) associated defensive behaviors. Earlier findings showed that activation of serotonin (5-HT) 1A and 2A receptors in the DPAG inhibits escape expression, a panicolytic-like effect. Recently gathered evidence shows that different classes of antipanic drugs, such as the selective serotonin reuptake inhibitor antidepressant fluoxetine or the benzodiazepine alprazolam, enhance the inhibitory action of 5-HT upon these receptors. They also show that opioidergic mechanisms, through the activation of μ-receptors, contribute to this process. As with 5-HT, activation of GABAA or GABAB receptors, or cannabinoid type 1receptors as well as the tropomyosin-related kinase B receptors by brain-derived neurotrophic factor in the DPAG also inhibits escape expression. There is evidence that chronic antidepressant treatment, besides facilitating 5-HT/opioid neurotransmission, also increases brain-derived neurotrophic factor levels in this area with an impact on its panicolytic effect. On the other hand, facilitation of corticotrophin releasing factor- or cholecystokinin-mediated neurotransmission in the DPAG, via CRF1 and CCK2 receptors, respectively, causes panicogenic-like effects with implications for the pathogenesis of PD. A better understanding of the neurochemical control of defense in the DPAG may foster the development of new strategies for pharmacological treatment of PD.

Keywords: Anxiety, animal models, defensive behavior, dorsal periaqueductal gray, neurotransmitters, panic.

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Article Details

VOLUME: 14
ISSUE: 8
Year: 2015
Page: [988 - 995]
Pages: 8
DOI: 10.2174/1871527314666150909114558
Price: $58

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