Increased psychological responses and divergent neuroendocrine responses to m-CPP and ipsapirone in patients with panic disorder

In patients with panic disorder and/or agoraphobia (PDA) an increased sensi tivity of central 5-HT2C receptors and a decreased responsiveness of 5-HT1A receptors has been postulated. In the present study, neuroendocrine challe nges were performed using oral doses of the non-selective 5-HT2C agonist m- chlorophenylpiperazine (m-CPP) (0.4mg/kg), the selective 5-HT1A antagonist ipsapirone (0.3mg/kg), and placebo in 40 patients with PDA and 12 healthy c ontrols in order to compare 5-HT2C and 5-HT1A-specific psychobehavioural an d neuroendocrine response patterns. At baseline, all psychobehavioural vari ables and the plasma concentration of noradrenaline (NE) were significantly increased in the patient group compared to the controls. The administratio n of m-CPP or ipsapirone was followed by comparable psychological symptoms and, in 55% of all patients, panic attacks. In comparison to the control su bjects, patients were characterized by significantly higher psychological r eactions to both challenge agents and a significantly higher NE response to m-CPP. In the patient group, there was also a trend towards an increased c ortisol response after administration of m-CPP and a decreased cortisol and hypothermia response after administration of ipsapirone compared to the co ntrol group. The neuroendocrine findings of our study support earlier repor ts of opposite changes in the responsiveness of 5-HT2C- and 5-HT1A-related receptors in PDA patients. The behavioural hypersensitivity to both, m-CPP and ipsapiron, shows that the provocation of anxiety and other psychologica l symptoms might be influenced by cognitive factors. (C) 2000 Zippincott Wi lliams & Wilkins.