Serotonin-mediated cyclic AMP inhibitory pathway in platelets of patients affected by panic disorder

Cyclic adenosine monophosphate (cAMP) pathway abnormalities have been suggested to be involved in anxiety disorders including panic (PD). The present study sought at investigating the downstream inhibitory adenylyl cyclase (AC) pathway activated by 5-HT in platelets obtained from 22 patients with a diagnosis of PD versus 22 healthy volunteers. In PD patients, a significant impairment of 5-HT potency to inhibit AC was observed. One month of treatment with paroxetine induced a significant increase of 5-HT potency in T1 patients close to the control values. [(35)S]GTPgammaS binding studies showed that in PD patients, a reduction of 5-HT receptor-G protein coupling occurred without any significant changes in G protein levels. These findings demonstrated that (1) a reduction of the inhibitory AC pathway activated by 5-HT occurred in platelets from PD patients; (2) the reduced 5-HT responsiveness in PD was related to an impairment of 5-HT receptor-G protein coupling, and (3) after 1 month of treatment with paroxetine, such a dysfunction significantly reversed together with a significant improvement of clinical symptoms.