Role of dmCPu in acquisition and expression of nicotine CS evoked CR

描述（由申请人提供）：烟草使用是全世界可预防死亡的主要原因。这种习惯不仅对个人使用者而且对他们周围的人（二手烟）都是有害的。尼古丁是烟草制品的主要成瘾性成分，是一种强大的兴奋剂和强化剂。重要的是，除了它的无条件效应，尼古丁也有条件刺激效应，这可能有助于吸烟习惯的持久性。对尼古丁作为条件刺激的学习过程的研究是一个与尼古丁依赖相关的研究不足的领域。了解这些与尼古丁内感受作用相关的过程是很重要的，如果我们的目标是开发一个全面的

DESCRIPTION (provided by applicant): Tobacco use is the leading cause of preventable deaths worldwide. This habit is not only debilitating to individual users but also to those around them (second-hand smoking). Nicotine is the main addictive component of tobacco products and is a powerful stimulant and reinforcer. Importantly, besides its unconditional effects, nicotin also has conditional stimulus effects that may contribute to the tenacity of the smoking habit. Investigation of learning processes involving nicotine as a conditioned stimulus (CS) is an understudied area relevant to nicotine dependence. Understanding these associative processes with the interoceptive effects of nicotine is of importance if a goal is to develop a comprehensive theory of addiction and, hence, develop better prevention and treatment strategies. A preliminary study assessing neurobiological loci involved in nicotine-evoked CR found that activation (as revealed through elevation of c-Fos) of dmCPu was dependent on learning history with nicotine. The proposed research builds on this finding and is designed to elucidate functional involvement of dmCPu in the conditioning processes with nicotine as a CS. Because anatomical connections within anterior-posterior axis of the rat's dorsal striatum are not homogeneous and can differ in their control of conditioning processes, both anterior (a-dmCPu) and posterior (p-dmCPu) portions of dmCPu will be tested for their involvement in acquisition and expression of the nicotine-evoked CR. The current study will examine the effect of permanent neurotoxin lesions of either a- or p-dmCPu on acquisition of nicotine evoked CR, and the effect of transient lesions of either a- or p-dmCPu on the expression of the nicotine-evoked CR. In the first experiment, rats will receive lesions (NMDA) or sham lesions (vehicle) of either a-dmCPu or p-dmCPu before nicotine CS training. During nicotine CS training (32 total daily sessions), nicotine injections (0.4 mg/kg; SC) will be paired 100% of a time with intermittent (36 per session) sucrose deliveries; sucrose will not be available on alternative saline days. Using this protocol, the nicotine CS readily acquires control of a goal-tracking CR (anticipatory food-seeking response). Deficits in acquiring this nicotine- evoked CR (using this standard protocol) will indicate a region's involvement in acquisition of the CR to the nicotine CS. In the second experiment, rats will first undergo nicotine CS training (identical to Experiment 1) and then receive implantation of intracranial cannulae (a- or p-dmCPu). Rats will be bilaterally infused with either lidocaine or saline before testing for the nicotine-evoked CR. Attenuated CR during testing will indicate critical involvement of implicated area in the expression of the CR. Knowledge gained from these experiments will fill a gap in understanding regional neurobiological processes potentially contributing to the tenacity of tobacco dependence.