Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus

J Physiol. 2005 Dec 15;569(Pt 3):751-60. doi: 10.1113/jphysiol.2005.097477. Epub 2005 Oct 20.


Exogenous cannabinoids have been shown to significantly alter neuroendocrine output, presaging the emergence of endogenous cannabinoids as important signalling molecules in the neuroendocrine control of homeostatic and reproductive functions, including the stress response, energy metabolism and gonadal regulation. We showed recently that magnocellular and parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus and supraoptic nucleus (SON) respond to glucocorticoids by releasing endocannabinoids as retrograde messengers to modulate the synaptic release of glutamate. Here we show directly for the first time that both of the main endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), are released in an activity-dependent fashion from the soma/dendrites of SON magnocellular neurones and suppress synaptic glutamate release and postsynaptic spiking. Cannabinoid reuptake blockade increases activity-dependent endocannabinoid levels in the region of the SON, and results in the inhibition of synaptically driven spiking activity in magnocellular neurones. Together, these findings demonstrate an activity-dependent release of AEA and 2-AG that leads to the suppression of glutamate release and that is capable of shaping spiking activity in magnocellular neurones. This activity-dependent regulation of excitatory synaptic input by endocannabinoids may play a role in determining spiking patterns characteristic of magnocellular neurones under stimulated conditions.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Benzoxazines
  • Benzyl Compounds / pharmacology
  • Cannabinoid Receptor Modulators / metabolism*
  • Cannabinoids / pharmacology
  • Endocannabinoids*
  • Excitatory Postsynaptic Potentials / drug effects
  • Glutamic Acid / metabolism
  • Glycerides / metabolism
  • In Vitro Techniques
  • Male
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Presynaptic / drug effects
  • Receptors, Presynaptic / metabolism
  • Supraoptic Nucleus / drug effects
  • Supraoptic Nucleus / metabolism*
  • Synaptic Transmission / drug effects


  • Arachidonic Acids
  • Benzoxazines
  • Benzyl Compounds
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Glycerides
  • Morpholines
  • Naphthalenes
  • OMDM-2 cpd
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptors, Presynaptic
  • AM 251
  • Glutamic Acid
  • Win 55212-2
  • glyceryl 2-arachidonate
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide