title: Translational approach to the pathophysiology of panic disorder: Focus on serotonin and endogenous opioids.
abstract: Panic patients experience recurrent panic attacks. Two main neurochemical hypotheses have been proposed to explain this vulnerability. The first suggests that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organizes defensive reactions to cope with proximal threats as well as of sympathomotor control areas of the rostral ventrolateral medulla that generate neurovegetative symptoms of the panic attack. The second proposes that endogenous opioids buffer panic attacks in normal subjects, and their deficit results in heightened sensitivity to suffocation and separation anxiety in panic patients. Experimental results obtained in rat models of panic indicate that serotonin interacts synergistically with endogenous opioids in the dorsal periaqueductal gray through 5-HT1A and μ-opioid receptors to inhibit proximal defense and, supposedly, panic attacks. These findings allow reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology. They also indicate that endogenous opioids are likely to participate in the panicolytic action of antidepressants and suggest that exogenous opioids may be useful for treating panic patients resistant to conventional pharmacotherapy.
authors.affiliation: Institute of Neuroscience and Behavior - INeC, Avenida do Café, 2450, 14050-220 Ribeirão Preto, SP, Brazil; Neurobiology of Emotion Research Centre (NAP-NuPNE), University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address: hegog@hotmail.com.
authors.forename: Frederico G
authors.initials: FG
authors.lastname: Graeff
mesh_terms: D000701:Analgesics, Opioid; D000818:Animals; D006801:Humans; D018847:Opioid Peptides; D010200:Panic; D016584:Panic Disorder; D010487:Periaqueductal Gray; D012701:Serotonin
chemical_list: D000701:Analgesics, Opioid; D018847:Opioid Peptides; D012701:Serotonin
keywords: 5-HT1A receptor; Animal models; Endogenous opioids; Panic disorder; Periaqueductal gray matter; Proximal defense; Serotonin; μ-Opioid receptor