Scholarlink

Rationale <p>Chronic opioid use leads to long-term dysregulation of the systems related to reward, pain and stress. In recent years, much attention has been given to the role of endocannabinoid CB1 receptors in opioid-driven behaviors. However, neuroadaptations of these receptors following opioid exposure is less clear.</p> Objectives <p>In this study, we systematically assessed CB1 receptor protein expression within the cortico-mesolimbic-basal ganglia circuit in rats with a history of heroin exposure and assessed the involvement of CB1 receptors in heroin conditioned place preference (CPP).</p> Results <p>(1) During naloxone-precipitated withdrawal, heroin-treated rats showed significantly more withdrawal signs including rapid weight loss, wet dog shakes, abnormal posture, genital grooming and urination than saline control rats. Although heroin-treated rats scored higher on criteria pertaining to vocalization, defecation, jumping and profuse salivation than did saline-treated rats, these trends did not reach statistical significance. (2) Using Western Blotting, we found that there were significant decreases in CB1 receptor protein expression in the nucleus accumbens (NAc), hypothalamus (Hypoth), substantia nigra (SN) and pedunculopontine nucleus (PPT), but no changes in this protein were detected in the prefrontal cortex, insula, dorsal striatum, medial/lateral septi, amygdala, dorsal hippocampus, ventral tegmental area and lateral tegmental nucleus. 3). Intracranial microinjections of AM251 (a CB1 receptor antagonist) into the NAc, SN, Hypoth or PPT caused significant and dose-dependent reductions in heroin CPP.</p> Conclusions <p>These data suggest that CB1 receptors undergo region-specific neuroadaptation following chronic heroin exposure and are involved in heroin CPP.</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

Heroin-induced neuroadaptations of CB1 receptors and their involvement in conditioned place preference

  • 期刊论文

  • 发表日期：

    2026年1月22日

查看全文
  • Ewa Galaj,
  • Charlotte Morris,
  • Anna Fleischer,
  • Coco Xie,
  • Holly Shortell,
  • Joseph Slama,
  • Catherine Litchfield,
  • Sloan Petersohn,
  • Emma Burdick,
  • Kirk Persaud,
  • Sharnom Chowdhury,
  • Amadea Sulka,
  • Arthur Aminov,
  • Robert Ranaldi

摘要

Rationale

Chronic opioid use leads to long-term dysregulation of the systems related to reward, pain and stress. In recent years, much attention has been given to the role of endocannabinoid CB1 receptors in opioid-driven behaviors. However, neuroadaptations of these receptors following opioid exposure is less clear.

Objectives

In this study, we systematically assessed CB1 receptor protein expression within the cortico-mesolimbic-basal ganglia circuit in rats with a history of heroin exposure and assessed the involvement of CB1 receptors in heroin conditioned place preference (CPP).

Results

(1) During naloxone-precipitated withdrawal, heroin-treated rats showed significantly more withdrawal signs including rapid weight loss, wet dog shakes, abnormal posture, genital grooming and urination than saline control rats. Although heroin-treated rats scored higher on criteria pertaining to vocalization, defecation, jumping and profuse salivation than did saline-treated rats, these trends did not reach statistical significance. (2) Using Western Blotting, we found that there were significant decreases in CB1 receptor protein expression in the nucleus accumbens (NAc), hypothalamus (Hypoth), substantia nigra (SN) and pedunculopontine nucleus (PPT), but no changes in this protein were detected in the prefrontal cortex, insula, dorsal striatum, medial/lateral septi, amygdala, dorsal hippocampus, ventral tegmental area and lateral tegmental nucleus. 3). Intracranial microinjections of AM251 (a CB1 receptor antagonist) into the NAc, SN, Hypoth or PPT caused significant and dose-dependent reductions in heroin CPP.

Conclusions

These data suggest that CB1 receptors undergo region-specific neuroadaptation following chronic heroin exposure and are involved in heroin CPP.