Lausanne University Hospital-CHUV, Prilly, Switzerland.
Institut Des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France.
Psychopharmacology (Berl). 2022 Apr;239(4):1053-1063. doi: 10.1007/s00213-021-05987-5. Epub 2021 Oct 1.
Cocaine use not only depends on the reinforcing properties of the drug, but also on its pharmacological effects on alternative nondrug activities. In animal models investigating choice between cocaine and alternative sweet rewards, the latter influence can have a dramatic impact on choice outcomes. When choosing under cocaine influence is prevented by imposing sufficiently long intervals between choice trials, animals typically prefer the sweet reward. However, when choosing under the drug influence is permitted, animals shift their preference in favor of cocaine.
We previously hypothesized that this preference shift is mainly due to a direct suppression of responding for sweet reward by cocaine pharmacological effects. Here we tested this hypothesis by making rats tolerant to this drug-induced behavioral suppression.
Contrary to our expectation, tolerance did not prevent rats from shifting their preference to cocaine when choosing under the influence.
Thus, other mechanisms must be invoked to explain the influence of cocaine intoxication on choice outcomes.
可卡因的使用不仅取决于药物的强化特性,还取决于其对替代非药物活动的药理作用。在研究可卡因和替代甜味奖励之间选择的动物模型中,后者的影响会对选择结果产生巨大影响。当通过在选择试验之间施加足够长的间隔来阻止在可卡因影响下进行选择时,动物通常更喜欢甜味奖励。然而,当允许在药物影响下进行选择时,动物会改变偏好,倾向于可卡因。
我们之前假设这种偏好转变主要是由于可卡因的药理作用直接抑制了对甜味奖励的反应。在这里,我们通过使大鼠对这种药物诱导的行为抑制产生耐受性来检验这一假设。
与我们的预期相反,当在影响下进行选择时,耐受性并不能阻止大鼠将偏好转向可卡因。
因此,必须援引其他机制来解释可卡因中毒对选择结果的影响。