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  • Title: D2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry.
    Author: O'Neill C, Evers-Donnelly A, Nicholson D, O'Boyle KM, O'Connor JJ.
    Journal: J Neurochem; 2009 Feb; 108(3):545-51. PubMed ID: 19187091.
    Abstract:
    Cannabinoid CB(1) receptors are highly expressed in the striatum where they are known to be co-localized with dopamine D(2) receptors. There is now strong evidence that cannabinoids modulate dopamine release in the brain. Using fast cyclic voltammetry, single pulse stimulation (0.1 ms; 10 V) was applied every 5 min and peak dopamine release was measured with a carbon fibre microelectrode. Application of the D(2) receptor agonist, quinpirole, inhibited single pulse dopamine overflow in a concentration-dependent manner (IC(50): 3.25 x 10(-8) M). The CB(1) receptor agonist WIN55212-2 (WIN; 1 microM) had no effect on single pulse dopamine release (93.9 +/- 6.6% at 60 min, n = 5) but attenuated the inhibitory effect of quinpirole (30 nM; quinpirole 39.0 +/- 4.2% vs. quinpirole + WIN, 48.2 +/- 3.7%, n = 5, p < 0.05). This affect was antagonized by the CB(1) receptor antagonist [N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (AM-251, 1 microM). Dopamine release evoked by four pulses delivered at 1 Hz (4P1Hz) and 10 pulses delivered at 5 Hz (10P5Hz) was significantly inhibited by WIN [72.3 +/- 7.9% control (peak 4 to 1 ratio measurement) and 66.9 +/- 3.8% control (area under the curve measurement), respectively, p < 0.05; n = 6 for both]. Prior perfusion of WIN significantly attenuated the effects of quinpirole on multiple pulse-evoked dopamine release (4P1Hz: quinpirole, 28.4 +/- 4.8% vs. WIN + quinpirole, 52.3 +/- 1.2%; 10P5Hz: quinpirole, 29.5 +/- 1.3% vs. WIN + quinpirole, 59.4 +/-7.1%; p < 0.05 for both; n = 6). These effects were also antagonized by AM-251 (1 microM). This is the first report demonstrating a functional, antagonistic interaction between CB(1) receptors and D(2) autoreceptors in regulating rat striatal dopamine release.
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