Intracranial Drug Self-administration

本项目的主要目标是通过使用颅内自我给药程序来表征大脑中的化学强化回路。在过去的一年里，我们进行了三项主要研究。首先，我们发现下丘脑后乳头上核的GABA能受体在初级强化中起重要作用。大鼠将学会将GABA-A受体拮抗剂印防己毒素或荷包牡丹碱自行注入乳突上核，这表明乳突上核是奖赏回路的一部分。其次，我们检查了尼古丁在腹侧被盖区(VTA)及其周围强化作用的准确部位。我们发现，大鼠学会了向VTA后部、中央线状核和乳突上核自我给予尼古丁，而它们并不容易学会向这些区域之间及其周围的区域自我给予尼古丁，包括VTA前部、黑质、VTA后部背侧区域、脚间核或乳头状内侧核。因此，尼古丁强化涉及VTA内和周围的多个区域。第三，我们得到的结果表明，目前腹侧纹状体分为伏隔核和壳层以及嗅结节，并不能反映苯丙胺奖赏的功能组织。大鼠很快学会将D-苯丙胺自行注入内侧壳或内侧结节，而不是轻易学会进入伏隔核、腹侧壳或外侧结节。我们的结果表明，苯丙胺的初级强化是通过腹侧纹状体的内侧部分介导的。因此，内侧壳和内侧结节在功能上比内侧和腹侧壳或内侧和外侧结节更相关。根据最近的解剖学数据和这些功能发现，应该重新考虑目前的核-壳-结节方案。这些发现为大脑如何组织初级强化提供了重要信息。

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.