Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate uptake.
Activation of cannabinoid CB1 receptors reduces glutamatergic synaptic transmission in the rodent striatum and is involved in the normal control of motor function by the basal ganglia. Here we investigated CB1 receptor regulation of glutamate release and uptake and synaptic transmission in the rat striatum. We show that CB1 receptor activation reduces both the release and uptake of [3H]glutamate in striatal slices. We also demonstrate that both activation of CB1 receptors and inhibition of glutamate uptake reduce corticostriatal synaptic transmission in a mutually occlusive manner and that both forms of depression are dependent on metabotropic glutamate receptor (mGluR) activation. We propose that CB1 receptor activation in the striatum decreases glutamate transporter activity and that the resulting increase in synaptic cleft glutamate concentration causes the activation of presynaptic mGluRs, which then decrease glutamate release.
Brown
Timothy M
TM
School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.
Brotchie
Jonathan M
JM
Fitzjohn
Stephen M
SM
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D013759:Dronabinol / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D002186:Cannabinoids; C114624:LY 341495; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C103505:AM 251; D018698:Glutamic Acid; D013759:Dronabinol; D000077285:Rimonabant