Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells

J Physiol. 1998 Aug 1;510 ( Pt 3)(Pt 3):867-79. doi: 10.1111/j.1469-7793.1998.867bj.x.


1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity. 2. Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716-A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and the paired-pulse facilitation of these PF-mediated EPSCs increased in the presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716-A. The same impairment of LTD was produced by 2-chloroadenosine, a compound that decreases the probability of release of glutamate at PF-PC synapses. 7. The present study demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines
  • Calcium Channel Blockers / pharmacology
  • Cannabinoids / pharmacology*
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / drug effects*
  • Cyclohexanols / pharmacology
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • In Vitro Techniques
  • Male
  • Membrane Potentials / physiology
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Nerve Fibers / drug effects
  • Neuronal Plasticity / drug effects*
  • Patch-Clamp Techniques
  • Piperidines / pharmacology
  • Purkinje Cells / drug effects*
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rimonabant
  • Synaptic Transmission / drug effects*


  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoids
  • Cyclohexanols
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Rimonabant