release of dopamine is associated with the subjective sensation of the so-called high.36 This is because fast and steep increases in dopamine activate low-affi nity dopamine D1 receptors, which are necessary for the rewarding effects of drugs37 and for triggering conditioned responses.38 By contrast, dopamine stimulation of high-affi nity dopamine D2 receptors is not suffi cient for drug reward,39,40 and these receptors might even limit drug reward.41 In this respect, drugs emulate the increases in dopamine triggered by phasic dopamine firing, which are the firing frequencies of dopamine neurons associated with rewarding stimuli.42
