Characterize the patterns of reginal brain activation produced by intravenous infusions of alpha2 adrenergoc agonist (clonidine 2ug/kg) and antagonist (yohimbine 0.4 mg/kg) drugs in healthy controls. Characterize the temporal relationship between fMRI signal change in regions of cortex and thalamus known to have high concentrations of NE and fMRI signal change in the pontine region containing the LC and other adrenergic nuclei. Correlate the temporal onset of fMRI signal changes to the onset of physiologic and behavioral changes induced by the alpha2 agonist and antagonist drugs. Characterized the effects of intravenous clonidine and yohimbine on cortical fMRI signals evoked by two sensory activation paradigms, the first a moving visual stimulus that will activate occipital cortex, the second a somatosensory stimulation that will activate frontoparietal cortex. Both cortical areas are known to have high NE concentration. Develop specific cognitive activation paradigms to selectively increase fMRI signal intensity in the inferior temporal lobe, an area with very low NE innervation and in the frontoparietal cortex, an area with dense NE innervation. Characterize the effects of intravenous clonidine and yohimbine on inferior temporal lobe cortical activation by this paradigm and constrast with cognitive activation of frontoparietal cortex. Determine the effect of opiate dependence on fMRI activation patterns induced by intravenous challenge of clonidine and yohimbine at rest and after sensory activation of frontoparietal and occipital cortex. Determine the effect of clonidine/buprenorphine rapid detoxification treatment on fMRI activation patterns in opiate dependent subjects.
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