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:Institute of Neuroscience and Behavior (INeC), 14049-900, Ribeirão Preto, SP, Brazil.
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.
