Intracranial Drug Self-administration

点击翻译按钮获取中文摘要

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.