Pharmacological activation of kappa opioid receptors in the nucleus accumbens core and ventral tegmental area increases the aversive effects of nicotine

Abstract

Aversive effects of nicotine play an important role in the development of nicotine dependence. However, neural substrates and/or brain regions that play a role in the aversive effects of nicotine have not been fully identified. Previous work done in our laboratory showed that systemic administration of kappa opioid receptors (KORs) agonist ±U50488 increased the aversive effects of nicotine. In this study, we assessed the effects of KOR activation in specific brain regions, namely, the nucleus accumbens (NAcc) core and ventral tegmental area (VTA) on the aversive effects of nicotine using the conditioned taste aversion model. Separate groups of Wistar rats were implanted with cannulae above either the NAcc core or the VTA. KOR agonist (±U50488) was bilaterally infused in the NAcc core (0, 0.3, and 3 ug/0.5 ul/side) or VTA (0, 0.3, 1.5, and 3 ug/0.5 ul/side) prior to receiving nicotine (0.4 mg/kg, base; s.c.) during conditioning. Bilateral infusion of the KOR agonist (3 ug/0.5 ul/side) in the NAcc core or the VTA increased the aversive effects of nicotine compared with respective saline controls. Together, these results suggest that pharmacological activation of the KORs in the NAcc core and VTA dose dependently modulate the aversive effects of nicotine. Because aversive effects of nicotine determine susceptibility to development of nicotine dependence, we can conclude that KOR activity in the NAcc and VTA after administration of nicotine may determine susceptibility to the development of nicotine dependence.