Scholarlink

Rationale <p>Available data suggest that α5GABAA receptors play an important role in the regulation of impulsive behavior.</p> Objectives <p>We studied the effect of selective positive and negative modulation of α5GABAA receptors, alone and in combination with NMDA receptor blockade, on different areas of impulsivity in rats.</p> Methods <p>A modified variable delay-to signal (VDS) paradigm in touchscreen chambers was introduced and validated. Male rats pretrained in the VDS protocol were treated with MK-801 at different doses and subjected to a test consisting of 20 initial 6-second delay trials, followed by 60 variable delay trials of 9–15&#xa0;s, and finally 20 6-second delay trials. The dose of 0.05&#xa0;mg/kg MK-801 in combination with 10&#xa0;mg/kg GL-II-73 or 5&#xa0;mg/kg PWZ-029 was tested in the VDS paradigm and the elevated plus maze to assess the potential of their interaction in the areas of impulsivity and anxiety, respectively.</p> Results <p>The principal component analysis revealed three dimensions of impulsivity, assignable to motor impulsivity, delay intolerance and reflective impulsivity. Delay intolerance and reflective impulsivity elicited by 0.05&#xa0;mg/kg MK-801 were more likely to affect high-impulsive rats than low-impulsive rats. The low MK-801 dose did not replicate the impulsive effect in the interaction experiment, while the addition of GL-II-73 resulted in significant delay intolerance. The same doses of tested compounds did not affect emotional reactivity.</p> Conclusions <p>The proimpulsive effect of positive modulation of α5GABAA receptors on delay intolerance can be interpreted as a kind of cognitive influence, but also as favoring reward seeking due to increased motivation, which requires further research.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Influences of subtle NMDA receptor blockade and allosteric modulation of α5 GABAA receptors on reward-related impulsivity in rats

  • 期刊论文

  • 发表日期：

    2026年5月11日

查看全文
  • Jovana Aranđelović,
  • Bojan Batinić,
  • Dishary Sharmin,
  • Danijela Milenković,
  • Đorđe Đorović,
  • V. V. N. Phani Babu Tiruveedhula,
  • James M Cook,
  • Miroslav M Savić

摘要

Rationale

Available data suggest that α5GABAA receptors play an important role in the regulation of impulsive behavior.

Objectives

We studied the effect of selective positive and negative modulation of α5GABAA receptors, alone and in combination with NMDA receptor blockade, on different areas of impulsivity in rats.

Methods

A modified variable delay-to signal (VDS) paradigm in touchscreen chambers was introduced and validated. Male rats pretrained in the VDS protocol were treated with MK-801 at different doses and subjected to a test consisting of 20 initial 6-second delay trials, followed by 60 variable delay trials of 9–15 s, and finally 20 6-second delay trials. The dose of 0.05 mg/kg MK-801 in combination with 10 mg/kg GL-II-73 or 5 mg/kg PWZ-029 was tested in the VDS paradigm and the elevated plus maze to assess the potential of their interaction in the areas of impulsivity and anxiety, respectively.

Results

The principal component analysis revealed three dimensions of impulsivity, assignable to motor impulsivity, delay intolerance and reflective impulsivity. Delay intolerance and reflective impulsivity elicited by 0.05 mg/kg MK-801 were more likely to affect high-impulsive rats than low-impulsive rats. The low MK-801 dose did not replicate the impulsive effect in the interaction experiment, while the addition of GL-II-73 resulted in significant delay intolerance. The same doses of tested compounds did not affect emotional reactivity.

Conclusions

The proimpulsive effect of positive modulation of α5GABAA receptors on delay intolerance can be interpreted as a kind of cognitive influence, but also as favoring reward seeking due to increased motivation, which requires further research.