Panic disorder - A malfunction of multiple transmitter control systems within the midbrain periaqueductal gray matter?

The clinical and psychopharmacological profile of panic disorder in human patients shows a remarkable similarity to the defensive behavioral response evoked in experimental animals by activation of neurons in the dorsal part of the midbrain periaqueductal gray matter (PAG). Studies of the neural circuitry within the PAG indicate that a subpopulation of GABAergic neurons in the dorsolateral sector may act as an amplifying stage that potentiates inhibitory serotonergic input to the "defense area" within the PAG. These neurons may function as a gain-control system that sets the level of excitability of efferent output neurons, which mediate the autonomic and somatomotor components of panic behavior. Dysfunctional activity within the dorsolateral PAG leading to a destabilization of this control system may be a factor underlying panic behavior and predisposes to the development of panic disorder in susceptible persons.