Mead Andy N, Crombag Hans S, Rocha Beatriz A
Behavioural Neuroscience Branch, The National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
Neuropsychopharmacology. 2004 Feb;29(2):249-58. doi: 10.1038/sj.npp.1300294.
Incentive motivation theory ascribes a critical role to reward-associated stimuli in the generation and maintenance of goal-directed behavior. Repeated psychomotor stimulant treatment, in addition to producing sensitization to the psychomotor-activating effects, can enhance the incentive salience of reward-associated cues and increase their ability to influence behavior. In the present study, we sought to investigate this incentive sensitization effect further by developing a model of conditioned reinforcement (CR) in the mouse and investigating the effects of a sensitizing treatment regimen of amphetamine on CR. Furthermore, we assessed the role of contextual stimuli in amphetamine-induced potentiation of CR. We found that mice responded selectively on a lever resulting in the presentation of a cue previously associated with 30% condensed milk solution, indicating that the cue had attained rewarding properties. Prior treatment with amphetamine (4 x 0.5 mg/kg i.p.) resulted in psychomotor sensitization and enhanced subsequent responding for the CR. Furthermore, this enhancement of responding for the cue occurred independent of the drug-paired context, whereas the sensitized locomotor response was only observed when mice were tested in the same environment as that in which they had received previous amphetamine. These results demonstrate that the CR paradigm previously developed in the rat can be successfully adapted for use in the mouse, and suggest that behavioral sensitization to amphetamine increases the rewarding properties (incentive salience) of reward-paired cues, independent of the drug-paired context.
激励动机理论认为，与奖励相关的刺激在目标导向行为的产生和维持中起着关键作用。反复给予精神运动性兴奋剂治疗，除了会使机体对精神运动激活效应产生敏化外，还能增强与奖励相关线索的激励显著性，并提高它们影响行为的能力。在本研究中，我们试图通过建立小鼠条件性强化（CR）模型并研究苯丙胺敏化治疗方案对CR的影响，进一步探究这种激励敏化效应。此外，我们评估了情境刺激在苯丙胺诱导的CR增强中的作用。我们发现，小鼠在一个杠杆上选择性地做出反应，从而呈现出一个先前与30%炼乳溶液相关的线索，这表明该线索具有奖励性质。预先给予苯丙胺（4×0.5mg/kg腹腔注射）导致精神运动敏化，并增强了随后对CR的反应。此外，对该线索反应的增强独立于与药物配对的情境，而只有当小鼠在与它们先前接受苯丙胺的相同环境中进行测试时，才观察到敏化的运动反应。这些结果表明，先前在大鼠中建立的CR范式可以成功地适用于小鼠，并表明对苯丙胺的行为敏化增加了与奖励配对线索的奖励性质（激励显著性），且独立于与药物配对的情境。
