In order to clarify the involvement of central noradrenergic systems and the nature of the alterations in behavioral responses to environmental stimuli produced acutely by hallucinogenic drugs, we propose to extend our studies of the effects of lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and 2,5-dimethoxy-4-methylamphetamine (DOM) to include more indoleamine and phenylethylamine hallucinogens, specifically, psilocybin, 2,5-dimethoxy-4-ethylamphetamine (DOET), and mescaline. The behavioral effects of these hallucinogens in male rats will be thoroughly characterized and compared using measures of tactile startle responses and a computerized Behavioral Pattern Monitor that provides detailed information regarding the amount and qualitative patterning of spontaneous activity and investigatory responses to specifiable familiar and novel stimuli in the environment. Rates of habituation of startle and exploration and the animal's sensitivity to novelty will be explicitly measured. The effects of selective neurotoxic lesions of specific noradrenergic pathways in brain will be similarly characterized. The effectiveness and specificity of each lesion will be quantified by both microspectrofluorimetric measures of formaldehyde-induced monoamine fluorescence and high-performance liquid chromatographic assays of regional monoamine levels using electrochemical detection. The possible mediation of the hallucinogen's effects by noradrenergic systems will be examined by testing the hallucinogens in lesioned animals and following pretreatments with selective antagonists or agonists, such as propranolol or clonidine. To minimize the confounding effects on the peripheral sympathetic nervous system, the adrenergic agonists and antagonists will be slowly infused into specific forebrain regions such as the hippocampus concurrently with the behavioral measures. The behavioral effects of these drugs will also be assessed to further delineate the influences of noradrenergic systems on activity, habituation, and responsiveness to exteroceptive stimuli. This work should further our understanding of the basic neural mechanisms mediating the behavioral effects of these drugs of abuse, eventually facilitating the development of antagonists for their effects.