RGD Reference Report - D2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry. - Rat Genome Database

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D2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry.

Authors: O'Neill, C  Evers-Donnelly, A  Nicholson, D  O'Boyle, KM  O'Connor, JJ 
Citation: O'Neill C, etal., J Neurochem. 2009 Feb;108(3):545-51.
RGD ID: 2314679
Pubmed: (View Article at PubMed) PMID:19187091
DOI: Full-text: DOI:10.1111/j.1471-4159.2008.05782.x

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-py razole-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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cnr1  (cannabinoid receptor 1)


Additional Information