Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzoxazines
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Cannabinoids / pharmacology
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Electric Stimulation
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Evoked Potentials / physiology
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Morpholines / pharmacology*
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Naphthalenes / pharmacology*
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Neurons / drug effects
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Neurons / physiology*
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Patch-Clamp Techniques
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Rats
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Rats, Sprague-Dawley
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Receptors, Cannabinoid
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Receptors, Drug / agonists
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Receptors, Drug / physiology*
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Substantia Nigra / drug effects
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Substantia Nigra / physiology*
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Synapses / drug effects
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Synapses / physiology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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gamma-Aminobutyric Acid / pharmacology
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gamma-Aminobutyric Acid / physiology*
Substances
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Benzoxazines
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Cannabinoids
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Morpholines
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Naphthalenes
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Receptors, Cannabinoid
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Receptors, Drug
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gamma-Aminobutyric Acid
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone