Background Among psychostimulants, the dopamine transporter ligands amphetamine and cocaine display the highest addictive potential; the adenosine receptor antagonist caffeine is most widely consumed but less addictive. Psychostimulant actions of amphetamine were correlated with its ability to orchestrate ventral tegmental dopamine neuron activity with contrasting shifts in firing after single vs repeated administration. Whether caffeine might impinge on dopamine neuron activity has remained elusive. Methods Population activity of ventral tegmental area dopamine neurons was determined by single-unit extracellular recordings and set in relation to mouse behavior in locomotion and conditioned place preference experiments, respectively. Results A single dose of caffeine reduced population activity as did amphetamine and the selective adenosine A2A antagonist KW-6002, but not the A1 antagonist DPCPX. Repeated administration of KW-6002 or amphetamine led to drug-conditioned place preference and to unaltered or even enhanced population activity. Recurrent injection of caffeine or DPCPX, in contrast, failed to cause conditioned place preference and persistently reduced population activity. Subsequent to repetitive drug administration, re-exposure to amphetamine or KW-6002, but not to caffeine or DPCPX, was able to reduce population activity. Conclusions Behavioral sensitization to amphetamine is attributed to persistent activation of ventral tegmental area dopamine neurons via the ventral hippocampus. Accordingly, a switch from acute A2A receptor-mediated reduction of dopamine neuron population activity to enduring A1 receptor-mediated suppression is correlated with tolerance rather than sensitization in response to repeated caffeine intake.

中文翻译：

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咖啡因对腹侧被盖区多巴胺神经元群活动的协调：与安非他明的比较

背景 在精神兴奋剂中，多巴胺转运体配体安非他明和可卡因具有最高的成瘾潜力。腺苷受体拮抗剂咖啡因消费最广泛，但成瘾性较低。安非他明的精神兴奋作用与其协调腹侧被盖多巴胺神经元活动的能力相关，并在单次和重复给药后产生对比鲜明的放电变化。咖啡因是否会影响多巴胺神经元的活动仍然难以捉摸。方法腹侧被盖区多巴胺神经元的群体活性通过单单元细胞外记录确定，并分别与小鼠在运动和条件位置偏好实验中的行为相关。结果 单剂量的咖啡因降低了群体活性，苯丙胺和选择性腺苷 A2A 拮抗剂 KW-6002 也如此，但 A1 拮抗剂 DPCPX 没有。反复服用 KW-6002 或安非他明会导致药物调节的位置偏好，并导致未改变甚至增强的人口活动。相比之下，反复注射咖啡因或 DPCPX 未能导致条件性位置偏好和人口活动持续减少。在重复给药后，再次接触安非他明或 KW-6002，而不是咖啡因或 DPCPX，能够减少人口活动。结论 对苯丙胺的行为敏感性归因于通过腹侧海马体持续激活腹侧被盖区多巴胺神经元。因此，