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

被引:7
作者
Graeff, Frederico Guilherme [1 ]
Sant'Ana, Ana Beatriz [2 ]
Vilela-Costa, Heloisa Helena [2 ]
Zangrossi, Helio, Jr. [2 ]
机构
[1] Inst Neurosci & Behav INeC, BR-14049900 Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeirao Preto, BR-14049 Ribeirao Preto, Brazil
关键词
Anxiety; animal models; defensive behavior; dorsal periaqueductal gray; neurotransmitters; panic; ELEVATED T-MAZE; CORTICOTROPIN-RELEASING-FACTOR; PANIC-LIKE RESPONSE; GREY-MATTER; CHOLECYSTOKININ-2; RECEPTORS; ENDOCANNABINOID SYSTEM; ELECTRICAL-STIMULATION; CANNABINOID RECEPTOR; SEROTONERGIC NEURONS; ANTIDEPRESSANT-LIKE;
D O I
10.2174/1871527314666150909114558
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 mu-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.
引用
收藏
页码:988 / 995
页数:8
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