TY - JOUR T1 - Stress-Induced Activation of the Dynorphin/κ-Opioid Receptor System in the Amygdala Potentiates Nicotine Conditioned Place Preference JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1488 LP - 1495 DO - 10.1523/JNEUROSCI.2980-11.2012 VL - 32 IS - 4 AU - Jeffrey S. Smith AU - Abigail G. Schindler AU - Emma Martinelli AU - Richard M. Gustin AU - Michael R. Bruchas AU - Charles Chavkin Y1 - 2012/01/25 UR - http://www.jneurosci.org/content/32/4/1488.abstract N2 - Many smokers describe the anxiolytic and stress-reducing effects of nicotine, the primary addictive component of tobacco, as a principal motivation for continued drug use. Recent evidence suggests that activation of the stress circuits, including the dynorphin/κ-opioid receptor system, modulates the rewarding effects of addictive drugs. In the present study, we find that nicotine produced dose-dependent conditioned place preference (CPP) in mice. κ-Receptor activation, either by repeated forced swim stress or U50,488 (5 or 10 mg/kg, i.p.) administration, significantly potentiated the magnitude of nicotine CPP. The increase in nicotine CPP was blocked by the κ-receptor antagonist norbinaltorphimine (norBNI) either systemically (10 mg/kg, i.p.) or by local injection in the amygdala (2.5 μg) without affecting nicotine reward in the absence of stress. U50,488 (5 mg/kg, i.p.) produced anxiety-like behaviors in the elevated-plus maze and novel object exploration assays, and the anxiety-like behaviors were attenuated both by systemic nicotine (0.5 mg/kg, s.c.) and local injection of norBNI into the amygdala. Local norBNI injection in the ventral posterior thalamic nucleus (an adjacent brain region) did not block the potentiation of nicotine CPP or the anxiogenic-like effects of κ-receptor activation. These results suggest that the rewarding effects of nicotine may include a reduction in the stress-induced anxiety responses caused by activation of the dynorphin/κ-opioid system. Together, these data implicate the amygdala as a key region modulating the appetitive properties of nicotine, and suggest that κ-opioid antagonists may be useful therapeutic tools to reduce stress-induced nicotine craving. ER -