Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Biology Department, William Paterson University, Wayne, New Jersey, USA.
Int J Neuropsychopharmacol. 2024 Feb 1;27(2). doi: 10.1093/ijnp/pyae001.
Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to nonpharmacological and pharmacological stimuli, with addictive psychostimulants being the most effective drugs that elicit calling behavior in rats. Earlier investigations found that dopamine D1-like and D2-like receptors modulate the emission of 50-kHz USVs stimulated in rats by the acute administration of addictive psychostimulants. Conversely, information is lacking on how dopamine D1-like and D2-like receptors modulate calling behavior in rats that are repeatedly treated with addictive psychostimulants.
We evaluated the emission of 50-kHz USVs in rats repeatedly treated (×5 on alternate days) with amphetamine (1 mg/kg, i.p.) either alone or together with (1) SCH 23390 (0.1-1 mg/kg, s.c.), a dopamine D1 receptor antagonist; (2) raclopride (0.3-1 mg/kg, s.c.), a selective dopamine D2 receptor antagonist; or (3) a combination of SCH 23390 and raclopride (0.1 + 0.3 mg/kg, s.c.). Calling behavior of rats was recorded following pharmacological treatment, as well as in response to the presentation of amphetamine-paired cues and to amphetamine challenge (both performed 7 days after treatment discontinuation).
Amphetamine-treated rats displayed a sensitized 50-kHz USV emission during repeated treatment, as well as marked calling behavior in response to amphetamine-paired cues and to amphetamine challenge. Antagonism of D1 or D2 receptors either significantly suppressed or attenuated the emission of 50-kHz USVs in amphetamine-treated rats, with a maximal effect after synergistic antagonism of both receptors.
These results shed further light on how dopamine transmission modulates the emission of 50-kHz USVs in rats treated with psychoactive drugs.
大鼠对非药物和药物刺激会发出 50-kHz 超声波(USVs),而成瘾性精神兴奋剂是最有效的药物,可以诱发大鼠的叫声行为。早期的研究发现,多巴胺 D1 样和 D2 样受体调节大鼠急性给予成瘾性精神兴奋剂刺激后 50-kHz USVs 的发射。相反,关于多巴胺 D1 样和 D2 样受体如何调节反复给予成瘾性精神兴奋剂的大鼠的叫声行为的信息却缺乏。
我们评估了反复给予安非他命(1mg/kg,ip)(×5 次,隔日一次)的大鼠中 50-kHz USVs 的发射,要么单独给予,要么与以下药物一起给予:(1)SCH 23390(0.1-1mg/kg,sc),多巴胺 D1 受体拮抗剂;(2)raclopride(0.3-1mg/kg,sc),一种选择性多巴胺 D2 受体拮抗剂;或(3)SCH 23390 和 raclopride 的组合(0.1+0.3mg/kg,sc)。在药物治疗后以及在呈现安非他命配对线索和安非他命挑战(均在治疗停止后 7 天进行)时,记录大鼠的叫声行为。
反复给予安非他命的大鼠在反复治疗期间显示出 50-kHz USVs 发射的敏感化,以及对安非他命配对线索和安非他命挑战的明显叫声行为。D1 或 D2 受体的拮抗剂要么显著抑制或减弱安非他命处理大鼠的 50-kHz USVs 的发射,在两种受体的协同拮抗作用后达到最大效果。
这些结果进一步阐明了多巴胺传递如何调节接受精神活性药物治疗的大鼠中 50-kHz USVs 的发射。