Endocrine Responses after d-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality

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Abstract
The tridemensional model of personality introduced by Cloninger relates aspects of novelty seeking to the dopaminergic, harm avoidance (HA) to the serotonergic, and reward dependence to the noradrenergic neurotransmitter system. Using a neuroendocrine challenge paradigm, this study investigates whether subjects characterized by blunted cortisol (CORT) responses after ipsapirone (IPS) relate to different subfactors of HA from those characterized by blunted prolactin (PRL) responses after treatment with d-fenfluramine (D-FEN). Moreover, subjects blunted in both responses should differ in scale values of subfactors of HA from those with only one or no blunted reactions. In the first part of the experiment, 16 healthy male volunteers were treated with 15 mg D-FEN. The second part of the study (about 1 year later) consists of a challenge with the partial 5-hydroxytryptamine-1a (5-HT1a) agonist IPS (10 mg) in the same subjects. The results indicate that blunted PRL responses are accompanied by high values in HA, while the main effect of IPS responsivity did not relate significantly to this dimension. With respect to the subscales of HA, subjects blunted in both responses (PRL–/C–) exhibit significantly higher levels in fatigability and asthenia when compared to all other groups (PRL–/C+, PRL+/C–,PRL+/C+). The data demonstrate that combined challenge tests may shed more light on the biological basis of personality and that HA and most clearly fatigability and asthenia relate to the 5-HT system.