Amphetamine acts within the medial basal forebrain to initiate and maintain alert waking

Amphetamine-like stimulants exert well-known arousal-enhancing actions. Surprisingly, little is known concerning the neuroanatomical substrates through which these drugs enhance arousal. Previous work implicates a number of basal forebrain structures in the regulation of behavioral state. The current studies examined the effects of amphetamine infusions made directly within basal forebrain sites on behavioral, electroencephalographic, and electromyographic indices of arousal in anesthetized and unanesthetized rat. In the anesthetized rat, amphetamine elicited prolonged epochs of bilateral electroencephalographic activation when infused unilaterally (3.75 microg/150 nl) into an extended region of the medial basal forebrain, demarcated anteriorally by the anterior portion of the medial septal area (which includes posterior accumbens shell) and posteriorally by the posterior aspect of the preoptic area of the hypothalamus. In the unanesthetized (undisturbed, resting) rat, amphetamine infusions into this region elicited prolonged epochs of alert waking, which at the lowest dose (3.75 microg), qualitatively resembled normal waking. Infusions placed lateral (including within the substantia innominata), anterior (including within the core subregion of the nucleus accumbens), posterior, or dorsal to these structures, as well as directly within the lateral ventricles did not alter electroencephalographic or behavioral measures. These results indicate that a region of the medial basal forebrain, extending from the anterior medial septum/accumbens shell to the posterior preoptic area, is a site within which amphetamine-like stimulants act to enhance behavioral and electroencephalographic measures of arousal.