Abstract: This invention pertains to the discovery that a dopamine receptor agonist can activate PKA signaling and/or can act synergistically with an adenosine receptor to activate such signaling. In various embodiments, this invention exploits the synergy between the dopamine receptor pathway and an adenosine receptor pathway to provide methods of mitigating one or more symptoms produced by the chronic consumption of a substance of abuse or to mitigate one or more physiological and/or behavioral symptoms associated with cessation of chronic consumption of a substance of abuse. In certain embodiments, the methods involve administering to the mammal an effective amount of an adenosine receptor antagonist; and an effective amount of a dopamine receptor antagonist; where the effective amount of the adenosine receptor antagonist is lower than the effective amount of an adenosine receptor antagonist administered without said dopamine receptor antagonist.

Abstract: Alcohol-related disorders are treated by the administration of adenosine antagonists and adenosine agonists to a host. Adenosine antagonists are used to inhibit both acute intoxication and chronic dependence by administering prior to alcohol consumption. The symptoms associated with alcohol withdrawal syndrome may be treated by administering adenosine agonists which reduce the physiological dependence on alcohol during the withdrawal period.