It has been suggested that noradrenergic signaling may play a key role in mediating both reinforcement by and relapse to various drugs of abuse. This view is supported by evidence that clonidine attenuates symptoms associated with short-term opiate (Gold & Pottash, 1981), alcohol (Björkqvist, 1975), and nicotine (Glassman, Jackson, Walsh, Roose, & Rosenfeld, 1984) withdrawal in humans. For example, clonidine decreases craving, anxiety, tension, irritability, and restlessness associated with nicotine withdrawal (Glassman et al., 1984). More recently, administration of clonidine or other α2-adrenergic receptor agonists (e.g., lofexidine, guanfacine, guanabenz) has been demonstrated to attenuate stress-induced reinstatement of opiate, cocaine, and alcohol seeking in rats (Erb et al., 2000; Highfield, Yap, Grimm, Shalev, & Shaham, 2001; Lé et al., 2005; Shaham et al., 2000). These results are consistent with evidence that blocking post-synaptic α1-adrenergic receptors with prazosin decreases consumption of cocaine, opiates, nicotine, and alcohol (Greenwell, Walker, Cottone, Zorrilla, & Koob, 2009; Rasmussen et al., 2009; Simpson et al., 2009; Villégier, Lotfipour, Belluzzi, & Leslie, 2007; Wee, Mandyam, Lekic, & Koob, 2008; Zhang & Kosten, 2005, 2007) and with the findings of the current study that inhibiting noradrenergic signaling with the α2-adrenergic receptor agonist, clonidine, decreases voluntary alcohol consumption.
