ABSTRACT
Title
Effect of adenosine A2A receptor ligands on voluntary ethanol intake in msP rats
Authors
MV. Micioni Di B, C. Cifani, C. Lambertucci, R. Volpini, G. Cristalli, M. Massi
School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
Abstract
Adenosine A2A receptors (A2AARs) are largely co-expressed with dopamine D2 receptors (D2DRs) in the central nervous system. Stimulation of A2AARs elicits opposite effects to D2DR activation at the level of second messengers and early-gene expression.
Since dopaminergic neurotransmission may have an important role in the reinforcing properties of ethanol, the present study investigated the effect of the A2AAR agonists, CGS21680 and VT7, and an A2AAR antagonist, ANR94 [1] on voluntary 10% alcohol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Ethanol was offered 2 h/day at the beginning of the dark phase of the cycle and drugs were administered by intraperitoneal injection, 30 min before access to it.
The acute administration of CGS21680 or VT7, at doses of 0.1 or 0.3 mg/kg, induced a dose-dependent reduction in alcohol intake, whereas ANR94, 5 but not 1 mg/kg, induced a significant increase in ethanol intake, that was evident also during a subchronic treatment.
When the A2AAR antagonist ANR94, 1 mg/kg, was administered 5 min before CGS21680, 0.1 mg/kg, the attenuation of ethanol intake induced by CGS21680 was completely abolished.
These results indicate that A2AAR agonists induce a pronounced reduction of ethanol intake in msP rats and the effect of CGS21680 is completely abolished by an A2AAR antagonist, providing evidence that it is completely mediated by this receptor subtype. These findings suggest that A2AAR may represent an interesting target for the pharmacological treatment of alcoholism.
[1] Cristalli G et al. (2008) Current Pharmaceutical Design 14:1525-1552
Since dopaminergic neurotransmission may have an important role in the reinforcing properties of ethanol, the present study investigated the effect of the A2AAR agonists, CGS21680 and VT7, and an A2AAR antagonist, ANR94 [1] on voluntary 10% alcohol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Ethanol was offered 2 h/day at the beginning of the dark phase of the cycle and drugs were administered by intraperitoneal injection, 30 min before access to it.
The acute administration of CGS21680 or VT7, at doses of 0.1 or 0.3 mg/kg, induced a dose-dependent reduction in alcohol intake, whereas ANR94, 5 but not 1 mg/kg, induced a significant increase in ethanol intake, that was evident also during a subchronic treatment.
When the A2AAR antagonist ANR94, 1 mg/kg, was administered 5 min before CGS21680, 0.1 mg/kg, the attenuation of ethanol intake induced by CGS21680 was completely abolished.
These results indicate that A2AAR agonists induce a pronounced reduction of ethanol intake in msP rats and the effect of CGS21680 is completely abolished by an A2AAR antagonist, providing evidence that it is completely mediated by this receptor subtype. These findings suggest that A2AAR may represent an interesting target for the pharmacological treatment of alcoholism.
[1] Cristalli G et al. (2008) Current Pharmaceutical Design 14:1525-1552