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.