Serotonin in anxiety and panic: Contributions of the elevated T-maze

• Escape and inhibitory avoidance in the ETM are pharmacologically distinct reactions.
• MRN, but not DRN, 5-HT neurons selectively regulate inhibitory avoidance in the ETM.
• Panicolytic drugs facilitate 5-HT-mediated neurotransmission in the dPAG.
• 5-HT2C receptors in BLA mediate the acute anxiogenesis caused by antidepressants.
• dPAG 5-HT1A and μ-opioid receptors cooperatively modulate escape expression.

The elevated T-maze (ETM) was developed to test the hypothesis that serotonin (5-HT) plays an opposing role in the regulation of defensive behaviors associated with anxiety and panic. This test allows the measurement in the same rat of inhibitory avoidance acquisition, related to generalized anxiety disorder, and of one-way escape, associated with panic disorder. The evidence so far reported with the ETM supports the above hypothesis and indicates that: (1) whereas 5-HT neurons located at the dorsal raphe nucleus are involved in the regulation of both inhibitory avoidance and escape, those of the median raphe nucleus are primarily implicated in the former task; (2) facilitation of 5-HT1A- and 5-HT2A-mediated neurotransmission in the dorsal periaqueductal gray (dPAG) is likely to mediate the panicolytic drug action; (3) stimulation of 5-HT2C receptors in the basolateral amygdala increases anxiety and is implicated in the anxiogenesis caused by short-term administration of antidepressant drugs, and (4) 5-HT1A and the μ-opioid receptors work together in the dPAG to modulate escape or panic attacks. These last results point to the possible benefits of adjunctive opioid therapy for panic patients resistant to antidepressants that act on 5-HT neurotransmission.