Intracranial Drug Self-administration

本项目的主要目标是利用颅内自我给药程序来表征大脑中的化学强化回路。在过去一年，我们进行了三项主要研究。首先，我们发现下丘脑后乳头体上核的GABA能受体在初级强化中起重要作用。大鼠将学会自我管理GABA-A受体拮抗剂印防己毒素或荷包牡丹碱进入乳头上核，这表明乳头上核是奖励回路的一部分。其次，我们研究了尼古丁在腹侧被盖区（VTA）及其周围的强化作用的精确部位。我们发现，大鼠学会了自我管理尼古丁进入后腹侧被盖区，中央线性核，和乳头体上核，而他们不容易学会自我管理尼古丁进入这些区域之间和周围的区域，包括前腹侧被盖区，黑质，背侧的区域刚刚到后腹侧被盖区，脚间核，或内侧乳头体核。因此，尼古丁强化涉及腹侧被盖区及其周围的多个区域。第三，我们已经得到的结果表明，目前的腹侧纹状体划分成杏仁核和壳和嗅结节并不反映安非他明奖励的功能组织。大鼠很快学会将D-苯丙胺自我注射到内侧壳或内侧结节中，而它们不容易学会将D-苯丙胺注射到腹侧壳或外侧结节中。我们的研究结果表明，安非他明的主要加强介导的腹侧纹状体的内侧部分。因此，内侧壳和内侧结节比内侧壳和腹侧壳或内侧结节和外侧结节在功能上更相关。根据最近的解剖学数据和这些功能发现，应重新考虑目前的核-壳-结节方案。这些发现提供了关于大脑如何组织初级强化的重要信息。

Major goal of the present project is to characterize chemical reinforcement circuitry in the brain, with the use of intracranial self-administration procedures. In the past year, we conducted three major studies. First, we have found that GABAergic receptors in the supramammillary nucleus of the posterior hypothalamus play important roles in primary reinforcement. Rats will learn to self-administer the GABA-A receptor antagonist picrotoxin or bicuculline into the supramammillary nucleus, suggesting that the supramammillary nucleus is part of reward circuitry. Secondly, we examined precise sites of reinforcement action of nicotine in and around the ventral tegmental area (VTA). We found that rats learn to self-administer nicotine into the posterior VTA, central linear nucleus, and supramammillary nucleus, whereas they do not readily learn to self-administer nicotine into regions lying between and around these regions including the anterior VTA, substantia nigra, the region just dorsal to the posterior VTA, interpeduncular nucleus, or medial mammillary nucleus. Thus, nicotine reinforcement involves multiple regions in and around the VTA. Thirdly, we have obtained results suggesting that the current division of the ventral striatum into the accumbens core and shell and the olfactory tubercle does not reflect the functional organization for amphetamine reward. Rats quickly learn to self-administer D-amphetamine into the medial shell or medial tubercle, while they do not readily learn to do so into the accumbens core, ventral shell, or lateral tubercle. Our results suggest that primary reinforcement of amphetamine is mediated via the medial portion of the ventral striatum. Thus, the medial shell and medial tubercle are more functionally related than the medial and ventral shell or the medial and lateral tubercle. The current core-shell-tubercle scheme should be reconsidered in light of recent anatomical data and these functional findings. These findings provide important information as to how the brain is organized with respect to primary reinforcement.