Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
J Psychopharmacol. 2024 Nov;38(11):1025-1041. doi: 10.1177/02698811241268894. Epub 2024 Aug 12.
Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and-based on previous findings with amphetamine-their possible dependence on beta-adrenergic receptors.
Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1-10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3).
In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated.
With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity.
欣快的精神兴奋剂的作用机制仍知之甚少。 在成年大鼠中，积极的情绪状态与 50-kHz 超声发声（USVs）的变化有关：具体来说，“颤音”叫声比“平板”叫声更常见。 在这里，我们研究了急性和重复可卡因给药的影响，以及基于先前对安非他命的发现，它们可能对β肾上腺素能受体的依赖性。
成年雄性长耳大仓鼠接受腹腔内药物或盐水注射，然后每天进行 USV 记录。 分析了 14 种 50-kHz 叫声亚型。 在实验 1 和 2 中，单独测试了可卡因（1-10mg/kg）和普萘洛尔（10mg/kg）。 在实验 3 中，在条件性位置偏好（CPP）程序中寻找普萘洛尔/可卡因的相互作用。 实验 4 研究了急性和慢性可卡因作用（第 1 阶段），以及普萘洛尔/可卡因在开放场（第 2 阶段）或 CPP 程序（第 3 阶段）中的相互作用。
在未接受药物的动物中，可卡因增加了 50-kHz 叫声的频率，并且快速产生了敏化作用。 在更长时间的暴露后，可卡因现在也增加了颤音与平板叫声的相对流行度；还揭示了对其他亚型的影响。 β阻断剂普萘洛尔既不能预防可卡因 CPP，也不能预防可卡因对 USV 发射或运动的影响，但单独给药时却具有明显的 USV 相关作用。 CPP 幅度和 USV 相关措施之间没有相关性。
通过长期腹腔内给药，可卡因可以改变几种 50-kHz 叫声亚型的相对流行度；它促进颤音与平板叫声的能力特别符合积极情绪的解释。 可卡因的行为作用（即与 USV 相关的、运动的、CPP）似乎独立于β肾上腺素能受体活性。
