Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist.
Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata (SNR) neurones in rat midbrain slices to investigate the electrophysiological effects of cannabinoids. The cannabinoid receptor agonist WIN 55212-2 (10 microM) significantly reduced intranigrally evoked and spontaneous inhibitory post-synaptic currents (IPSCs) which were mediated by GABA(A) receptors. The postsynaptic current induced by bath application of GABA was not affected by the presence of WIN 55212-2. The actions of WIN 55212-2 were not mimicked by the inactive enantiomer WIN 55212-3. WIN 55212-2 also hyperpolarized the membrane of SNR neurones in a tetrodotoxin/0-Ca2+-insensitive manner. These data suggest that cannabinoids modulate the activity of SNR neurones by presynaptic inhibition of GABA inputs. They may also exert a direct post-synaptic inhibition on these neurones.
Chan
P K
PK
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin.
Chan
S C
SC
Yung
W H
WH
D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone