The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei

Eur J Neurosci. 2005 Jun;21(11):2958-66. doi: 10.1111/j.1460-9568.2005.04131.x.

Abstract

The suprachiasmatic nuclei (SCN) contain a major circadian pacemaker, which is regulated by photic and nonphotic stimuli. Although enkephalins are present in the SCN, their role in phase regulation of the pacemaker is largely unknown. The opioid agonist fentanyl, a homologue of morphine, is an addictive drug that induces phase shifts of circadian rhythms in hamsters. We observed that these phase shifts are blocked by naloxone, which is a critical test for true opioid receptor involvement, and conclude that opioid receptors are the sole mediators of the actions of fentanyl on the circadian timing system. A strong interaction between opioids and light input was shown by the ability of fentanyl and light to completely block each other's phase shifts of behavioural activity rhythms. Neuronal ensemble recordings in vitro provide first evidence that SCN cells show direct responses to fentanyl and react with a suppression of firing rate. Moreover, we show that fentanyl induces a strong attenuation of light-induced Syrian hamster Period 1 (shPer1) gene expression during the night. During the subjective day, we found no evidence for a role of shPer1 in mediation of fentanyl-induced phase shifts. Based on the present results, however, we cannot exclude the involvement of shPer2. Our data indicate that opioids can strongly modify the photic responsiveness of the circadian pacemaker and may do so via direct effects on SCN electrical activity and regulation of Per genes. This suggests that the pathways regulating addictive behaviour and the circadian clock intersect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / genetics
  • Animals
  • Behavior, Animal / drug effects
  • Cell Cycle Proteins
  • Chronobiology Disorders / chemically induced
  • Chronobiology Disorders / genetics
  • Chronobiology Disorders / metabolism
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics
  • Cricetinae
  • Fentanyl / adverse effects*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • In Situ Hybridization
  • Light Signal Transduction / drug effects*
  • Light Signal Transduction / genetics
  • Male
  • Mesocricetus
  • Narcotic Antagonists / pharmacology
  • Narcotics / adverse effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Nuclear Proteins / genetics*
  • Opioid-Related Disorders / genetics
  • Opioid-Related Disorders / metabolism
  • Opioid-Related Disorders / physiopathology
  • Organ Culture Techniques
  • Period Circadian Proteins
  • Photic Stimulation
  • Suprachiasmatic Nucleus / drug effects*
  • Suprachiasmatic Nucleus / metabolism
  • Suprachiasmatic Nucleus / physiopathology
  • Transcription Factors / genetics

Substances

  • Cell Cycle Proteins
  • Narcotic Antagonists
  • Narcotics
  • Nuclear Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Transcription Factors
  • Fentanyl