Given the confounds associated with CB1 agonists, it is not surprising that most data supporting the role of CB1 in mediating the rewarding effects of ethanol have been obtained by studies using genetic and pharmacological inactivation of CB1 signaling. Arnone et al (1997) published the earliest account of CB1 modulation of ethanol consumption, where they reported that SR treatment blocked both ethanol and sucrose solution intake in C57BL/6 mice. This report was followed by others indicating that systemic SR treatment reduced ethanol intake in several preclinical models of ethanol consumption. SR administration reduced the break-point in progressive ratio self-administration experiments where rats were trained to lever press for beer (Gallate and McGregor, 1999) or 10% ethanol solution (Economidou et al., 2006) indicating that blockade of the CB1 receptor decreased the reward value of ethanol. A study of operant responding for sipper tube access found that SR treatment reduced responding for both ethanol and sucrose (Freedland et al., 2001). Economidou et al (2006) reported a similar dose-dependent reduction in sucrose- and ethanol-associated lever presses following SR treatment, and this effect was
