Although less well developed, evidence exists for a role of norepinephrine systems in the extended amygdala in the negative motivational state and increased self-administration associated with dependence. Norepinephrine functional antagonists (β1 antagonist and α2 agonist) injected into the lateral bed nucleus of the stria terminalis blocked precipitated opiate withdrawal-induced place aversions (Delfs et al., 2000). The effects of norepinephrine in mediating the motivational effects of opioid withdrawal involve the ventral noradrenergic system. Ventral noradrenergic bundle lesions attenuated opioid withdrawal-induced place aversions (Delfs et al., 2000), but virtually complete lesions of the dorsal noradrenergic bundle from the locus coeruleus with the neurotoxin 6-hydroxydopamine failed to block the place aversion produced by opioid withdrawal (Caille et al., 1999). Functional norepinephrine antagonists block excessive drug intake associated with dependence on ethanol (Walker et al., 2008), cocaine (Wee et al., 2008), and opioids (Greenwell et al., 2008b). A focal point for many of these effects is the extended amygdala but at the level of the bed nucleus of the stria terminalis. κ Dynorphin, an opioid peptide that binds to κ opioid receptors, has long
