Effects of propofol on conditioned place preference in male rats: Involvement of nitrergic system

Am J Drug Alcohol Abuse. 2018;44(2):167-174. doi: 10.1080/00952990.2017.1344681. Epub 2017 Jul 27.


Background: Drug-induced conditioned place preference (CPP) is linked to the addictive properties of the drug used. The number of studies that have investigated the effects of propofol on CPP is limited. Research findings suggest that nitric oxide (NO) might play an important role in substance use disorders.

Objectives: The present study sought to investigate the role of the nitrergic system on the rewarding effects of propofol by using the CPP protocol in rats.

Methods: The experiment followed habituation, pre-conditioning, conditioning, and post conditioning sessions. Male Wistar albino rats weighing 240-290 g were divided into eight groups: control (saline), propofol (10, 20, and 40 mg/kg), the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) alone (30 and 60 mg/kg), and in combination with propofol (30 and 60 mg/kg L-NAME plus 40 mg/kg propofol) (n = 8 for each group). The CPP effects of propofol, L-NAME, saline, and their combinations were evaluated. All the drug and saline administrations were performed by intraperitoneal (ip) injections.

Results: Propofol (10-40 mg/kg) produced CPP that was statistically significant relative to saline. Propofol-induced CPP was significantly reversed by pretreatment with L-NAME. When administered alone, L-NAME did not produce CPP and also did not produce any significant change on locomotor activity of naïve rats.

Conclusion: Our results suggest that propofol produces CPP effects in rats and that NO-related mechanisms may be responsible for propofol-induced CPP. Thus, propofol might have the potential to be addictive, and this possibility should be considered during clinical applications of this drug.

Keywords: Addiction; L-NAME; conditioned place preference; nitric oxide; propofol; rat(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Locomotion / drug effects
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Propofol / antagonists & inhibitors
  • Propofol / pharmacology*
  • Rats
  • Reward


  • NG-Nitroarginine Methyl Ester
  • Propofol