Local administration of a cannabinoid agonist alters norepinephrine efflux in the rat frontal cortex

Neurosci Lett. 2008 Jan 24;431(1):1-5. doi: 10.1016/j.neulet.2007.11.009. Epub 2007 Nov 9.

Abstract

Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana, activates specific cannabinoid (CB) receptors to exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous research has demonstrated that systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal cortex. The distribution of CB1 receptors on noradrenergic fibers in the frontal cortex suggests this may be one potential site for the regulation of norepinephrine release. In the present study, we first examined the ability of a CB1 antagonist, applied locally in the frontal cortex of adult male Sprague-Dawley rats, to block the actions of systemic WIN 55,212-2. Pretreatment with SR 141716A (300 microM) significantly attenuated the excitatory effects of WIN 55,212-2 (15 mg/kg, i.p.). Next, the impact of direct perfusion of WIN 55,212-2 into the frontal cortex on extracellular norepinephrine efflux was measured. Direct application of WIN 55,212-2 (100 microM) into the frontal cortex elicited a significant increase in extracellular norepinephrine efflux suggesting that activation of cortical cannabinoid receptors contributes to alterations in norepinephrine levels in this brain region. Finally, local administration of SR 141716A followed by local administration of WIN 55,212-2 revealed a paradoxical inhibition of norepinephrine efflux.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzoxazines / pharmacology
  • Cannabinoids / agonists*
  • Cannabinoids / antagonists & inhibitors
  • Drug Interactions / physiology
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Male
  • Microdialysis
  • Microinjections
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Norepinephrine / metabolism*
  • Piperidines / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / metabolism
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism
  • Rimonabant
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology
  • Time Factors
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant
  • Norepinephrine