New Findings on the Neurotransmitter Modulation of Defense in the Dorsal Periaqueductal Gray.
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.
Institute of Neuroscience and Behavior (INeC), 14049-900, Ribeirão Preto, SP, Brazil. hegog@hotmail.com.
Frederico Guilherme
FG
Graeff
Ana Beatriz
AB
Sant'Ana
Heloísa Helena
HH
Vilela-Costa
Hélio
H
Zangrossi
D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016584:Panic Disorder / Q000188:drug therapy / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*
D018377:Neurotransmitter Agents