Figure 3.

Comparisons and similarities between AAS and ethanol actions. Chronic AAS exposure [24,25] and withdrawal from ethanol [85,100–102] both result in increased anxiety-like behavior. Molecular and cellular studies suggest that both of these drugs of abuse impose similar changes in neural signaling along a shared template that includes reciprocal connections between structures in the extended amygdala [43] {including the nucleus accumbens shell [NAc(s)], the bed nucleus of the stria terminalis (BnST), and the central nucleus of the amygdala (CeA) and the dorsal raphe (DRN)}, as well as their connections with structures, such as the anterior hypothalamus (AH), ventrolateral nucleus of the hypothalamus, hippocampus and medial prefrontal cortex, that are pivotal for the expression of both anxiety and aggression (Figure 2). Although some molecular targets have not been assessed in all of these key regions for both classes of drugs, the available data converge to suggest potential mechanisms by which both AAS exposure and ethanol withdrawal (EtOH-w) augment the expression of corticotropin releasing factor (CRF) in key regions of the anxiety circuitry, including the BnST [24,103], the CeA [25,84,85,100–102], and the DRN [102]. AAS and/or alcohol-dependent changes in CRF may, in turn, alter classical neurotransmission mediated by both GABA_ARs [25,84,85] and glutamate (as assessed by vesicular glutamate transporter 2, VGLUT2) [36] and glutamate receptors (GluRs) [56,103–105]. Finally, AAS and alcohol may significantly alter the activity of 5-HT neurons in the DRN [106] through GABAergic afferents to this region [90,107]. These DRN neurons may reflect a crucial focal point in the control of anxiety because they provide greater than 50% of the serotonergic innervation to the forebrain [108], including regions such as the BnST [61,109] and the CeA [52], implicated in the expression of anxious states, and regions such as the AH that are crucial for the expression of aggression [10]. Mouse brain adapted from an image in the Magnetic Resonance Microimaging Neurological Atlas (MRM NeAt) Mouse Brain Database (http://brainatlas.mbi.ufl.edu/ImageGallery.php).