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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats
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Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats

机译：腺苷A2A / A1受体拮抗剂对大鼠自我给药可卡因动机的时间和性别依赖性影响

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摘要

Adenosine is an important neuromodulator, known to interact with both dopaminergic and glutamatergic systems to influence psychostimulant action. In the present study, we examined the effects of ATL444, a novel adenosine receptor antagonist, on motivation for cocaine in male and female rats. Adult male and female Sprague-Dawley rats were trained to self-administer cocaine (1.5 mg/kg/infusion) on a fixed-ratio 1 schedule with a daily maximum of 20 infusions. Following 5 consecutive sessions during which all 20 available infusions were obtained, motivation for cocaine (0.5 mg/kg/infusion) was assessed under a progressive ratio (PR) schedule, and once responding stabilized, the effect of treatment with ATL444 (0, 15, and 30 mg/kg, i.p.) was examined. As a control, we also assessed its effects on PR responding for sucrose. Binding studies revealed that ATL 444 was 3-fold, 25-fold, and 400-fold more selective for the A2A receptor as compared to A1, A2B, and A3 receptors, respectively. ATL444 produced a significant increase in motivation for cocaine on the day of treatment in females with a trend for an increase in males. In addition, over the two PR sessions following ATL444 treatment a significant decrease in responding was observed in males but not females. Responding for sucrose was unaffected by ATL444 treatment. Our results reveal that adenosine receptor blockade may mediate both acute increases in the reinforcing effects of cocaine, and longer term inhibitory effects on cocaine reinforcement that differ according to sex.
机译：腺苷是一种重要的神经调节剂，已知会与多巴胺能和谷氨酸能系统相互作用，从而影响心理刺激作用。在本研究中，我们研究了一种新型腺苷受体拮抗剂ATL444对雄性和雌性大鼠可卡因动机的影响。训练成年雄性和雌性Sprague-Dawley大鼠以固定比例1的时间表自我给药可卡因（1.5 mg / kg /输液），每天最多输注20次。在连续5次疗程中，获得了全部20种可用的输注液后，按照渐进比率（PR）方案评估了可卡因（0.5 mg / kg /输液）的动机，一旦反应稳定，就使用ATL444进行治疗（0，15 ，并检查30 mg / kg，ip）。作为对照，我们还评估了其对PR对蔗糖反应的影响。结合研究表明，与A1，A2B和A3受体相比，ATL 444对A2A受体的选择性分别高3倍，25倍和400倍。在女性接受治疗的当天，ATL444导致可卡因的动机显着增加，而男性则呈增加趋势。此外，在ATL444治疗后的两个PR疗程中，男性反应明显下降，而女性则没有。对蔗糖的反应不受ATL444处理的影响。我们的研究结果表明，腺苷受体阻滞剂可介导可卡因增强作用的急性增加，以及对可卡因增强作用的长期抑制作用，视性别而定。

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