This article reviews experimental evidence and theoretical constructs that implicate serotonin (5-HT) modulation of defensive behavior within the midbrain periaqueductal gray matter(PAG) in panic disorder. Results obtained with conflict tests in experimental animals indicate that 5-HT enhances anxiety, whereas results with aversive stimulation of the dorsal PAG point to an anxiolytic role of 5-HT. To solve this contradiction, it has been suggested that the emotional states determined by the two paradigms are different. Conflict tests would generate anticipatory anxiety, whereas PAG stimulation would produce fear as evoked by proximal threat. Clinically, the former would be related to generalized anxiety while the latter to panic disorder. Thus, 5-HT is supposed to facilitate anxiety, but to inhibit panic. This hypothesis has been tested in the animal model of anxiety and panic named the elevated T-maze and in two procedures of human experimental anxiety applied to healthy volunteers or panic patients. Overall, the obtained results have shown that drugs that enhance 5-HT action increase different indexes of anxiety, but decrease indexes of panic. Drugs that impair 5-HT action had the opposite effects. Thus, so far the predictions derived from the above hypothesis have been fulfilled. The main clinical implications are that a 5-HT deficit in the PAG may participate in the pathophysiology of panic disorder and that an enhancement of 5-HT in the same region mediates the anti-panic action of antidepressant drugs.
Animal models of anxiety; Human experimental anxiety; Serotonin modulation of defense; Neurobiology of panic disorder
