New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Abstract

Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

Effect of Zuogui Pill (左归丸) on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack

“…(12) Another study assumed that panic patients had defi cient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organizes defensive reactions to cope with proximal threats and that the rostral ventrolateral medulla that generates most symptoms of the panic attack. (13) Other evidence has indicated that 5-HT 1A receptors in the dorsal periaqueductal gray matter and 5-HT 2A receptors in the dorsolateral septum mediate panic behavior in the elevated T-maze. (14,15) Additionally, copious evidence has demonstrated that the NE system also acts as a main role in the pathogenesis of panic attack.…”

Lifelong Opioidergic Vulnerability Through Early Life Separation: A Recent Extension of the False Suffocation Alarm Theory of Panic Disorder

“…Moreira et al (2013) present a thoughtful review of the use of rodents in panic disorder research. Graeff (2012), studying an animal model of panic disorder found that the inhibitory action of serotonin is connected with activation of endogenous opioids in the periaqueductal gray (PAG). Schenberg and colleagues (Schimitel et al, 2012) suggest "[the PAG] harbors an anoxiasensitive suffocation alarm system".…”

Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder

“…Moreira et al (2013) present a thoughtful review of the use of rodents in panic disorder research. Graeff (2012), studying an animal model of panic disorder found that the inhibitory action of serotonin is connected with activation of endogenous opioids in the periaqueductal gray (PAG). Schenberg and colleagues (Schimitel et al, 2012) suggest “[the PAG] harbors an anoxia-sensitive suffocation alarm system”.…”