[Serotonin, periaqueductal gray matter and panic disorder]

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Biology

Context:

• The role of serotonin (5-HT) in defensive behaviors and its modulation within the midbrain periaqueductal gray (PAG) is complex and debated.
• Conflicting evidence exists regarding 5-HT's effects on anxiety versus fear, with some studies suggesting it enhances anxiety and others indicating an anxiolytic role.

Purpose:

• To review experimental evidence and theoretical frameworks implicating serotonin modulation of defensive behaviors in the PAG in panic disorder.
• To reconcile contradictory findings on 5-HT's role in anxiety and fear by differentiating between anticipatory anxiety and acute fear responses.

Summary:

• Experimental results indicate that 5-HT enhances anxiety in conflict tests but has an anxiolytic effect when stimulating the dorsal PAG.
• This dichotomy suggests 5-HT facilitates generalized anxiety while inhibiting panic, a hypothesis tested in animal models and human studies.
• Studies using the elevated T-maze and human experimental anxiety paradigms showed that drugs enhancing 5-HT increased anxiety but decreased panic, supporting the hypothesis.

Impact:

• Findings suggest a potential deficit in PAG serotonin contributes to panic disorder pathophysiology.
• Enhancing serotonin in the PAG may be the mechanism underlying the anti-panic effects of antidepressant medications.
• This research provides a neurobiological basis for understanding panic disorder and developing targeted treatments.