The purpose of this study is to investigate the role of brain receptors called alpha2-adrenoreceptors in regulating the sympathetic nervous system, which maintains the supply of blood and fuel to the body's organs in times of stress, fear, anger, or exercise. Alpha(2)-adrenergic receptors (alpha(2)-AR) play a role in a variety of physiological functions. There are three subtypes of alpha(2)-ARs, and their differences are unknown. This study will examine the functional roles of these three subtypes by comparing the behavioral, biochemical, psychophysiological, and autonomic function effects of the alpha(2)-AR drugs clonidine and yohimbine. Participants in this study will undergo a physical examination, electrocardiogram (ECG), and blood, urine, and saliva tests. Women will have hormone tests to determine the time of their last period and the time of their next ovulation. Participants will undergo neuropsychological testing and other procedures.

NCT00029627

Conditions

1. Healthy

Interventions

1. Drug: Yohimbine

Based on preclinical studies the following hypotheses will be tested: 1) subjects homozygous or heterozygous for the alpha(2)(A)-AR Asn251Lys substitution will show a potentiation of clonidine-induced effects, relative to subjects who have the Asn251/Asn251 genotype, and a reduction of yohimbine-induced effects, 2) subjects homozygous or heterozygous for a alpha(2)(B)-AR three glutamic acid deletion (residues 301-303) will show reduced effects of the alpha(2)-AR agonist clonidine and possibly a potentiation of effects of yohimbine, and 3) we will evaluate whether altered responses in either direction occur in subjects homozygous and heterozygous for an in-frame deletion of a alpha(2)(C)-AR homologous repeat occurring at codons 322-325 relative to subjects without this deletion allele. --- Asn251Lys ---