Bauer Clayton T, Banks Matthew L, Blough Bruce E, Negus S Stevens
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Behav Pharmacol. 2013 Sep;24(5-6):448-58. doi: 10.1097/FBP.0b013e328363d1a4.
'Rate dependency' in the discipline of behavioral pharmacology describes a phenomenon wherein the effect of a drug on the rate of a behavior varies systematically as a function of the baseline, predrug rate of that behavior. Historically, rate-dependency studies have compared drug effects on different baseline rates of behavior maintained either by different schedules of reinforcement or during sequential segments of a fixed-interval schedule. The current experiment generated different baseline rates of behavior by altering frequency of electrical stimulation in an intracranial self-stimulation assay. Amphetamine and 10 other monoamine releasers were analyzed for their ability to produce rate-dependent effects in this assay. There were three main findings. First, all compounds produced rate-dependent effects at some dose. Second, one parameter of rate-dependency plots (peak Y-intercept of the regression line) correlated with in-vitro neurochemical data on selectivity of these compounds to release dopamine versus serotonin (P<0.025, R=0.50). Lastly, a correlation between peak Y-intercept and breakpoints under a progressive-ratio procedure in nonhuman primates was also significant (P<0.05, R=0.64). Overall, these results extend the rate-dependent effects of monoamine releasers to behavior maintained under intracranial self-stimulation and suggest that, at least for monoamine releasers, the Y-intercept parameter of rate-dependency plots might be a useful metric of drug reward and predictor of drug self-administration measures of drug reinforcement.
行为药理学学科中的“速率依赖性”描述了一种现象，即药物对行为速率的影响会随着该行为的基线、用药前速率而系统地变化。从历史上看，速率依赖性研究比较了药物对通过不同强化程序维持的不同行为基线速率的影响，或者在固定间隔程序的连续时间段内的影响。当前的实验通过改变颅内自我刺激试验中的电刺激频率来产生不同的行为基线速率。分析了苯丙胺和其他10种单胺释放剂在该试验中产生速率依赖性效应的能力。有三个主要发现。首先，所有化合物在某些剂量下都产生了速率依赖性效应。其次，速率依赖性图的一个参数（回归线的峰值Y轴截距）与这些化合物释放多巴胺与血清素的选择性的体外神经化学数据相关（P<0.025，R=0.50）。最后，峰值Y轴截距与非人类灵长类动物在累进比率程序下的断点之间的相关性也很显著（P<0.05，R=0.64）。总体而言，这些结果将单胺释放剂的速率依赖性效应扩展到颅内自我刺激维持的行为，并表明，至少对于单胺释放剂来说，速率依赖性图的Y轴截距参数可能是药物奖赏的有用指标和药物强化的药物自我给药措施的预测指标。
