Critical role of the endogenous cannabinoid system in mouse pup suckling and growth

Eur J Pharmacol. 2001 May 11;419(2-3):207-14. doi: 10.1016/s0014-2999(01)00953-0.


Delta9-tetrahydrocannabinol, the active principle in marijuana, is a cannabinoid receptor agonist. Both the crude drug and delta9-tetrahydrocannabinol have been used as appetite promoters. The endogenous cannabinoid, arachidonoyl ethanolamide (anandamide), likewise a cannabinoid receptor agonist, has been shown to have the same effect. In contrast, the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide (SR141716A) reduces food intake. Here, we report that administration of SR141716A to newly born mouse pups (either a single administration on postnatal day 1, or daily for a week as of postnatal day 2) had a devastating effect on milk ingestion and growth. The first 24 h after birth appeared the most critical for the growth stunting effect of SR141716A. Death followed within 4-8 days. Co-administration of delta9-tetrahydrocannabinol almost fully reversed the effect of the antagonist in the week-long regimen. Co-administration of 2-arachidonoyl glycerol, an endocannabinoid, with 2-palmitoyl glycerol and 2-linoleoyl glycerol, which enhance 2-arachidonoyl glycerol potency, resulted in a significant delay in mortality rates caused by the antagonist. We conclude that the endocannabinoid system plays a vital role in milk suckling, and hence in growth and development during the early stages of mouse life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Appetite / drug effects*
  • Arachidonic Acids / pharmacology*
  • Cannabinoid Receptor Modulators
  • Chromatography, High Pressure Liquid
  • Dronabinol / pharmacology*
  • Endocannabinoids
  • Growth / drug effects
  • Mice
  • Milk / chemistry
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides
  • Pyrazoles / pharmacology*
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / antagonists & inhibitors*
  • Rimonabant


  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • Rimonabant
  • anandamide