Stimulant drug abuse is highly prevalent, constituting a major public health concern. To gain better insight into mechanisms contributing to stimulant drug abuse, the neurochemical mechanisms subserving the behavioral effects of these drugs have been intensively examined. Neurochemically, these drugs increase synaptic concentrations of dopamine (DA) and norepinephrine (NE). Evidence indicates that actions of DA within the striatum and nucleus accumbens are critical components of the rewarding and locomotor activating effects of stimulants. It is generally believed that NE serves a minimal contributory role in these behavioral actions of stimulants. However, recent observations by the PI indicate that previous studies may not have adequately addressed this issue. The rewarding effects of these drugs are superimposed upon an alert behavioral state (e.g. prolonged periods of waking/enhanced alertness). The ability of stimulants to maintain waking and enhance alertness has long been exploited and is a contributing factor to the widespread use of these drugs. However, the degree to which NE or DA participates in the """"""""arousal""""""""-enhancing actions of stimulants and which anatomical site(s) subserve such actions remains enigmatic. A variety of observations suggest that noradrenergic systems participates in the modulation of behavioral state. Previous studies by the PI demonstrated potent actions of the locus coeruleus (LC) on EEG and behavioral indices of waking via actions of beta-receptors located within structures located within the medial basal forebrain. Additional studies demonstrated potent arousal-enhancing effects of amphetamine when infused into these regions. These observations suggest that at least some of the arousal-enhancing actions of stimulants may be due to enhanced release of NE within the basal forebrain. Utilizing a combination of behavioral, pharmacological, and anatomical methods, the proposed studies will provide novel information concerning the degree to which NE participates in the behavioral effects of stimulants and the receptor mechanisms and circuitry involved in these actions. Information obtained in these studies may provide insight into mechanisms subserving, and treatment of, stimulant drug abuse.
Showing the most recent 10 out of 28 publications
