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

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

Volume: 14 Issue: 8

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

Affiliation:

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

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.

Cite this article as:

Graeff Guilherme Frederico, Sant'Ana Beatriz Ana, Vilela-Costa Helena Heloisa and Jr. Zangrossi Helio, New Findings on the Neurotransmitter Modulation of Defense in the Dorsal Periaqueductal Gray, CNS & Neurological Disorders - Drug Targets 2015; 14 (8) . https://dx.doi.org/10.2174/1871527314666150909114558