Corticosterone modulates dopamine and serotonin1A receptor mediated regulation of prepulse inhibition and startle in male rats

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-07-19 DOI:10.1016/j.neuropharm.2025.110594

Wendy K. Adams , Maarten van den Buuse

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Abstract

The aim of this project was to investigate the role of stress in neurotransmitter modulation of prepulse inhibition (PPI), a model of sensorimotor gating which is disrupted in schizophrenia and other illnesses. We studied the effect of adrenalectomy (ADX) and low and high levels of corticosterone (CORT) replacement on the effect of pharmacological modulators of PPI in rats. In ADX rats treated with a high dose of CORT (CORT200) the disruption of PPI caused by acute treatment with the dopamine receptor agonist, apomorphine, was significantly enhanced compared to ADX rats implanted with a control cholesterol pellet. On the other hand, CORT200 rats were less sensitive to the effect of the serotonin_1A receptor agonist, 8-OH-DPAT, while ADX rats implanted with a lower dose of CORT (CORT50) showed enhanced responding to this treatment. There were no differential effects on baseline PPI, or changes in startle or habituation of startle that could explain the effects on PPI. These data suggest that prolonged CORT treatment induces a major shift in dopaminergic and serotonergic mechanisms involved in the regulation of PPI. ADX and CORT replacement were found to have no effect on dopamine D₂ receptor densities in the nucleus accumbens (NAc), striatum or cingulate cortex, suggesting that our current observations are not due to changes in the levels of these receptors. These data may provide new insight into the role of stress in psychosis.

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皮质酮调节多巴胺和5 -羟色胺1a受体介导的雄性大鼠脉前抑制和惊吓的调节

这个项目的目的是研究压力在神经递质对预脉冲抑制（PPI）的调节中的作用，PPI是一种在精神分裂症和其他疾病中被破坏的感觉运动门控模型。我们研究了肾上腺切除术（ADX）和高低水平皮质酮（CORT）替代对大鼠PPI药理学调节剂作用的影响。在接受高剂量CORT （CORT200）治疗的ADX大鼠中，与植入对照胆固醇颗粒的ADX大鼠相比，多巴胺受体激动剂阿波啡急性治疗引起的PPI破坏显著增强。另一方面，CORT200大鼠对5 -羟色胺1a受体激动剂8-OH-DPAT的作用不太敏感，而植入较低剂量CORT （CORT50）的ADX大鼠对这种治疗的反应增强。对基线PPI没有差异影响，惊吓或惊吓习惯的变化也不能解释对PPI的影响。这些数据表明，长期CORT治疗可导致参与PPI调节的多巴胺能和血清素能机制发生重大转变。ADX和CORT替代对伏隔核（NAc）、纹状体或扣带皮层的多巴胺D2受体密度没有影响，这表明我们目前的观察结果不是由于这些受体水平的变化。这些数据可能为压力在精神病中的作用提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).