Involvement of dorsolateral periaqueductal gray cholecystokinin-2 receptors in the regulation of a panic-related behavior in rats

Cholecystokinin (CCK) has been implicated in anxiety disorders. The midbrain periaqueductal gray (PAG), which modulates anxiety and panic reactions, contains CCK-immunoreactive fibers and CCK2 receptors. The present study investigated the involvement of CCK2 receptors of the PAG dorsolateral subdivision (dlPAG) in the regulation of inhibitory avoidance and escape, two defensive behaviors that have been related in terms of psychopathology to generalized-anxiety and panic disorders, respectively. Male Wistar rats were microinjected in the dlPAG with the CCK2 receptor agonist cholecystokinin-tetrapeptide (CCK-4; 0.08-0.32 nmol/0.2 μL), the CCK2 receptor antagonist LY-225910 (0.05-0.20 nmol/0.2 μL) or LY-225910 prior to CCK-4. Inhibitory avoidance and escape behaviors were evaluated in the elevated T-maze. Whereas CCK-4 facilitated escape, indicating a panic-like action, LY-225910 had the opposite effect. Pretreatment with a non-effective dose of LY-225910 prevented the panic-eliciting action of CCK-4. Neither CCK-4 nor LY-225910 affected inhibitory avoidance acquisition. The present results substantiate the view that dlPAG CCK2 receptors modulate panic-related behaviors.