Multiple lines of evidence suggest that blockade of CBI receptors reduces reward-seeking. However, the reported effects of CBI blockade on performance for rewarding electrical brain stimulation stand out as an exception. By applying a novel method for conceptualizing and measuring reward seeking, we provide evidence consistent with reward-attenuating effects of cannabinoid receptor blockade: AM-2SI, a CBI receptor antagonist, decreases the willingness of rats to pay for medial forebrain bundle stimulation. This analysis clarifies inconsistencies between prior reports, which likely arose from: a) the averaging of data across subjects showing heterogeneous effects and b) the use of methods that cannot distinguish changes in the sensitivity of the reward substrate from changes in reward-substrate gain, reward costs and the value of competing activities such as grooming, resting, and exploring. The results link endocannabinoids to the roles of the latter three factors in reward seeking rather than to the modulation of reward sensitivity
