that are a general feature of biological systems also act to limit reward.4 Multiple circuits are likely to contribute to the hypothesised opponent-like processes. During acute withdrawal from all drugs of abuse, CRF increases in the extended amygdala (tables 1, 2, circuit 6). Importantly, CRF receptor antagonists block both the anxiety-like, stress-like effects of drug withdrawal and excessive drug taking during compulsive drug seeking in animals. Equally compelling, κ opioid receptor antagonists, when injected into the nucleus accumbens shell, can block the development of compulsive drug seeking (tables 1, 2, circuit 8).76–78 Decreases in the release of dopamine in the nucleus accumbens can also be driven by increases in the activity of the dynorphin-κ opioid receptor system in the ventral striatum and possibly increases in the activity of CRF in the ventral tegmental area, which contributes to the negative emotional state associated with withdrawal and protracted abstinence.20,21
