Endocannabinoid modulation of sympathetic and cardiovascular responses to acute stress in the periaqueductal gray of the rat

Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R771-9. doi: 10.1152/ajpregu.00391.2010. Epub 2011 Jan 12.

Abstract

Activation of the sympathetic nervous system is fundamental to the coordinated response to stress or danger. The midbrain periaqueductal gray (PAG) contains the neural substrate required to recruit the sympathetic nervous system and organize the physiological and behavioral responses required to respond to imposed challenges. Endocannabinoids have been shown to influence associated behavioral responses. The defense response was used in this study as a working model to examine endocannabinoid modulation of the sympathetic response to acute stress in the anesthetized rat. Microinjection of the cannabinoid 1 (CB1) receptor agonist anandamide into the defense pathway of the dorsal PAG could elicit an increase in renal sympathetic nerve activity and blood pressure, twitching of the whiskers, and movement of the limbs. The response was attenuated by prior microinjection of the CB1 receptor antagonist AM-281 at the same site. Electrical stimulation of the hypothalamic defense area could evoke similar sympathoexcitatory and pressor responses, which were significantly attenuated by microinjection of AM-281 into the dorsal PAG. These data indicate that endocannabinoids can modulate the sympathetic and cardiovascular components of the acute stress response via CB1 receptors at the level of the PAG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, General
  • Animals
  • Arachidonic Acids / administration & dosage
  • Blood Pressure
  • Cannabinoid Receptor Modulators / metabolism*
  • Cardiovascular System / innervation*
  • Electric Stimulation
  • Endocannabinoids*
  • Kidney / innervation*
  • Microinjections
  • Morpholines / administration & dosage
  • Motor Activity
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / metabolism*
  • Polyunsaturated Alkamides / administration & dosage
  • Pyrazoles / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Stress, Physiological*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism*
  • Time Factors

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cnr1 protein, rat
  • Endocannabinoids
  • Morpholines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 281
  • anandamide