Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy; National Institute of Neuroscience (INN), University of Cagliari, Cagliari, Italy.
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jun 8;108:110184. doi: 10.1016/j.pnpbp.2020.110184. Epub 2020 Nov 24.
Dopamine replacement therapy used in Parkinson's disease (PD) may induce alterations in the emotional state that can underlie the manifestation of iatrogenic psychiatric-like disturbances. The preclinical investigation of these disturbances is limited, also because few reliable paradigms are available to study the affective properties of dopaminomimetic drugs in parkinsonian animals. To provide a relevant experimental tool in this respect, we evaluated whether dopaminomimetic drugs modified the emission of 50-kHz ultrasonic vocalizations (USVs), a behavioral marker of positive affect, in rats bearing a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle. Apomorphine (2 or 4 mg/kg, i.p.), L-3,4-dihydroxyphenilalanine (L-DOPA, 6 or 12 mg/kg, i.p.), or pramipexole (2 or 4 mg/kg, i.p.) were administered in a test cage (× 5 administrations) on alternate days. Seven days after treatment discontinuation, rats were re-exposed to the test cage to measure conditioned calling behavior and thereafter received a drug challenge. Hemiparkinsonian rats treated with either apomorphine or L-DOPA, but not pramipexole, markedly vocalized during repeated treatment and after challenge, and showed conditioned calling behavior. Moreover, apomorphine, L-DOPA and pramipexole elicited different patterns of 50-kHz USV emissions and rotational behavior, indicating that calling behavior in hemiparkinsonian rats treated with dopaminomimetic drugs is not a byproduct of motor activation. Taken together, these results suggest that measuring 50-kHz USV emissions may be a relevant experimental tool for studying how dopaminomimetic drugs modify the affective state in parkinsonian rats, with possible implications for the preclinical investigation of iatrogenic psychiatric-like disturbances in PD.
用于帕金森病 (PD) 的多巴胺替代疗法可能会引起情绪状态的改变，从而导致医源性类似精神病障碍的表现。这些障碍的临床前研究受到限制，这也是因为很少有可靠的范式可用于研究帕金森病动物中拟多巴胺药物的情感特性。为了在这方面提供一个相关的实验工具，我们评估了多巴胺激动剂是否改变了携带内侧前脑束 6-羟多巴胺单侧损伤的大鼠的 50-kHz 超声发声 (USVs) 的发射，这是一种积极情绪的行为标志物。阿扑吗啡 (2 或 4 mg/kg，ip)、L-3,4-二羟基苯丙氨酸 (L-DOPA，6 或 12 mg/kg，ip) 或普拉克索 (2 或 4 mg/kg，ip) 在测试笼中 (× 5 次给药) 交替给药。治疗停止后 7 天，大鼠重新暴露于测试笼中以测量条件发声行为，然后接受药物挑战。用阿扑吗啡或 L-DOPA 治疗但不用普拉克索治疗的偏侧帕金森大鼠在重复治疗和挑战后明显发声，并表现出条件发声行为。此外，阿扑吗啡、L-DOPA 和普拉克索引起了不同模式的 50-kHz USV 发射和旋转行为，表明用拟多巴胺药物治疗的偏侧帕金森大鼠的发声行为不是运动激活的副产品。总之，这些结果表明，测量 50-kHz USV 发射可能是研究拟多巴胺药物如何改变帕金森病大鼠情感状态的一种相关实验工具，对研究 PD 中医源性类似精神病障碍的临床前研究具有潜在意义。
