Drugs of Abuse, Reward Comparison, and the Thalamus

滥用药物、奖励比较和丘脑

• 批准号: 7100734
• 负责人: Patricia Sue Grigson
• 金额: $ 28.94万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100734
• 关键词: behavioral /social science research tag; behavioral habituation /sensitization; cocaine; conditioning; dosage; drug abuse; drug addiction; electrophysiology; heroin; laboratory rat; morphine; neuroanatomy; operant conditionings; reinforcer; repression; self medication; sensory cortex; stimulus /response; substance abuse related behavior; sucrose; thalamus

DESCRIPTION (provided by applicant): Rats reduce intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse such as morphine or cocaine. This reduction in CS intake has led to the long standing assumption that drugs of abuse induce conditioned taste aversions via aversive properties. Papers published over the last funding period, however, argue against this account in support of the alternative hypothesis that rats avoid intake of the saccharin CS because they are anticipating the rewarding properties of the drug. Thus, published data now show that the suppressive effects of a rewarding sucrose solution, morphine, and cocaine, but not those of the aversive agent, LiCI, are similarly affected by the value of the CS, the deprivation state of the rat, the strain of the rat, a history of chronic morphine treatment, bilateral lesions of the gustatory thalamus, bilateral lesions of the gustatory cortex and, according to new preliminary data, unilateral asymmetric lesions of the gustatory thalamus and cortex. Lesions of the ventral tegmental area are without effect, but microdialysis data showed that accumbens dopamine clearly tracks drug-induced devaluation of the saccharin reward cue. Specific Aim 1 uses asymmetric lesions to test whether the suppressive effects of drugs and sweets, but not those of the aversive agent, LiCI, depend upon communication between the gustatory thalamus and cortex. Specific Aim 2 tests whether the lesion-induced disruption in cocaine suppression is mediated by the same selective memory/reward comparison deficit found with sucrose suppression. Finally, Specific Aim 3 tests whether accumbens dopamine depends upon an intact thalamocortical loop to track sucrose- and cocaine-, but not LiCI-induced suppression of CS intake. The overarching hypothesis is that this thalamo-cortical loop is required for the comparison of rewards over time, the resulting devaluation of the natural reward, and for the tracking of relative reward properties by the nucleus accumbens. If confirmed, we will have challenged the limits of the traditional "reward circuitry" and better elucidated the mechanisms of reward comparison.

描述（由申请人提供）：当与吗啡或可卡因等滥用药物配对时，大鼠减少了糖精条件刺激（CS）的摄入量。 CS摄入量的减少导致了一个长期的假设，即滥用药物通过厌恶性能引起条件味觉厌恶。然而，在最后一个资金期间发表的论文反对这一说法，以支持替代假设，即大鼠避免摄入糖精CS，因为它们正在期待该药物的有益特性。 Thus, published data now show that the suppressive effects of a rewarding sucrose solution, morphine, and cocaine, but not those of the aversive agent, LiCI, are similarly affected by the value of the CS, the deprivation state of the rat, the strain of the rat, a history of chronic morphine treatment, bilateral lesions of the gustatory thalamus, bilateral lesions of the gustatory cortex and, according to新的初步数据，味性丘脑和皮质的单侧不对称病变。腹侧对盖区域的病变无效，但是微透析数据表明，伏伏胺多巴胺清楚地跟踪了药物诱导的糖精奖励提示的贬值。特定的目标1使用不对称病变来测试药物和糖果的抑制​​作用，但不厌恶剂的lici的抑制作用是否取决于味觉丘脑和皮质之间的通信。特定的目标2测试是否通过与蔗糖抑制发现的相同的选择记忆/奖励比较缺陷介导了病变诱导的可卡因抑制中的破坏。最后，特定的目标3测试伏伏胺的多巴胺是否依赖于完整的丘脑皮质环，以跟踪蔗糖和可卡因 - 而不是Lici诱导的CS摄入抑制。总体假设是，随着时间的流逝，奖励的比较，自然奖励的贬值以及伏隔核对相对奖励性能的跟踪需要，需要这种丘脑形成环。如果得到确认，我们将挑战传统的“奖励电路”的限制，并更好地阐明奖励比较的机制。