hyperalgesia) and affective [anxiety-related behavior and conditioned place aversion (CPA)] nicotine withdrawal behaviors in C57BL/6J mice implanted with osmotic mini-pumps filled with nicotine or saline for 14 days (28 days for CPA). Withdrawal was initiated after 14 days of nicotine infusion or by removal of the mini-pumps. On day 15, mice were injected intracerebrovascularly with α6-selective antagonist α-conotoxin MII(H9A;L15A) and withdrawal signs were measured 10 min after injection. α-conotoxin MII(H9A;L15A) blocked withdrawal-associated CPA and anxiety-related behaviors (elevated plus maze) compared to mice injected intracerebroventricularly with saline, suggesting a role for the α6 subunit in affective nicotine withdrawal symptoms (Jackson et al. 2009). This study also demonstrated a role for the α6 subunit in nicotine reward, reflecting possible differences in nAChR subunit composition (α4α6β2* vs. α6β2* vs. α4α6α5β2*), different anatomical distribution of brain nAChRs, and/or different intracellular mechanism in nicotine reward and withdrawal (Jackson et al. 2009). α6* nAChRs are located in both the VTA and locus coeruleus. The VTA has been implicated in both nicotine reinforcement (Corrigall et al. 1992; Pons et al. 2008) and withdrawal (Bruijnzeel and Markou 2004) and the locus coeruleus has been implicated in withdrawal effects from drugs of abuse (Dizgah et al. 2005), implying that
