小分子NOP激动剂逆转可卡因诱导的运动运动敏感性在雄性C57BL/6小鼠中
Kabirullah Lutfy1, Abdul Hamid1, Nurulain T Zaveri2
1College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, United States of America.
Progress in neuro-psychopharmacology & biological psychiatry
|January 10, 2024
概括
小分子 nociceptin阿片类受体 (NOP) 激动剂在雄性小鼠中逆转了可卡因诱导的运动运动敏感性. 这些NOP激动剂对雌性小鼠没有影响,这表明对寻求药物行为的性别特异性影响.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 行为科学 行为科学
背景情况:
- 孤儿FQ/nociceptin (OFQ/N),是内源性联体的诺西素阿片类受体 (NOP),抑制可卡因诱导的运动器官敏感化.
- 之前的研究表明,OFQ/N有能力通过脑内静脉管内给药来阻断和逆转已建立的可卡因敏感性.
研究的目的:
- 调查是否系统地使用的小分子NOP激动剂可以复制OFQ/N.的抗敏化作用.
- 确定NOP激动剂在逆转可卡因诱导的运动器敏感性和防止其发展方面的有效性.
主要方法:
- 雄性小鼠表现出可卡因诱导的运动运动敏感性被用NOP激动剂 (AT-202,AT-524) 或载体治疗.
- 在可卡因挑战后评估了运动机动活动,以评估敏感性的逆转.
- 在NOP淘汰和野生型小鼠的实验中,研究了NOP受体在激动剂作用中的作用,包括性别差异.
主要成果:
- 在雄性小鼠中,NOP激动剂的亚慢性给药显著降低了已建立的运动运动敏感性.
- NOP激动剂AT-524在雄性野生型小鼠中逆转了敏感性,但在NOP淘汰小鼠中没有.
- 与可卡因同时使用NOP激活剂可以防止雄性野生型小鼠的敏感化发展,而雌性和NOP淘汰小鼠则没有这种效果.
结论:
- 小分子NOP激动剂可以逆转和预防可卡因诱导的雄性小鼠的运动器敏感性.
- 观察到的效应取决于功能性NOP受体的存在,并且似乎是性别特异性的,在雌性小鼠中没有发现任何效应.
相关概念视频
01:25Adrenergic Agonists: Indirect-Acting Agents
1.6K
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
1.6K
01:25Drug-Receptor Interaction: Agonist
2.5K
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
2.5K
01:22Opioid Receptors: Overview
847
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
847
01:29Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K