The goal of this research is to discover the most precise means of measuring individual differences in dopamine (DA) functioning, and then to test the relation of DA reactivity to personality traits. Using a pharmacological challenge protocol with hormonal and behavioral indicators as responses to tee challenge, several preliminary studies have demonstrated a strong relation between DA and extraversion or positive emotionality (PEM). The proposed study aims to establish a standard pharmacological challenge protocol that can be used by us and the scientific community to study DA, extraversion or PEM, and behavior. The most powerful means of expressing individual differences in DA trait levels is to assess the slope of DA reactivity across a series of incentive stimulus magnitudes -(i.e., DA-agonist challenge doses), providing a stimulus-DA dose-response function. The proposed study uses a randomized, cross-over design under double-blind conditions to establish a dose-response challenge protocol based on a set of 3 (out of 4) methylphenidate (MP) doses (iv .05, .15, .3, .5 mg/kg) as a function of sex. Indicators of MP effects are prolactin (PRL), growth hormone (GH), mood ratings, and working memory. Using the final 3 selected MP doses slope will be calculated across doses for each subject for each variable (GH, PRL, mood) to provide dose- response indicators of DA-reactivity to MP challenge. We will assess the extent to which the final set of indicators represents a similar MP-induced process by factor analyzing them in order to define one or more DA-reactivity factors. The DA-reactivity factor will then be intercorrelated with, first, the major personality traits, and, secondly, with the subdomains of the major traits that correlate significantly with DA reactivity. In this way, a """"""""DA"""""""" inventory will be derived. These studies are designed to enlighten several psychiatric problems that may involve a relation between DA and behavior. Recent research suggests that determination of DA- behavior relations could have benefit in understanding, and perhaps in treating, pathological forms of personality, especially of the Cluster B type, some forms of affective disorders, schizophrenic positive symptoms, and genetic-experience interactive liabilities to substance abuse that may depend on sensitivity of DA receptor types.
