Posted by djmmm on November 27, 2002, at 7:42:18
In reply to alcohol and stimulant effect, posted by jonh kimble on November 26, 2002, at 17:55:33
Alcohol is postulated to act by facilitating GABA-A function, by interacting with the GABA-A receptor, but at a site different from the GABA binding site or the benzodiazepine binding site. This results in the activation of the DA neurons in the mesolimbic system. This is involved in the sedative and anxiolytic effects and the rebound hyperexcitability seen during withdrawal.
The effect of alcohol on the DA system is not directly with the DA receptors, but rather indirectly by increasing DA levels in the mesocorticolimbic system. This increase is associated with the reinforcing and rewarding effects of alcohol
The interaction of alcohol with the opioid system is also indirect and results in activation of the opioid system. This is associated with reinforcing effects (probably via mu-receptors) and aversive effects (probably via kappa receptors). The opioid system is also involved in the craving for alcohol, and opioid antagonists, such as naloxone and naltrexone block the rewarding effects and craving for alcohol
Alcohol's effect on the NMDA system has also been studied. Alcohol inhibits the NMDA receptor, not by direct interaction with the glutamate binding site, but rather by modifying the way glutamate binds to its site on the receptor complex (allosteric effect). This interaction is thought to mediate the sedative/hypnotic effects of alcohol, as well as neuroadaptation. The NMDA system is also important in withdrawal.
The serotonin system is also thought to play a role in the pharmacology of alcohol. The mechanism for this is unknown, but thought to modulate DA release. What is known is that increasing serotonin levels at the synapse decreases alcohol intake. These data are mostly obtained in animal studies and need further investigation
Acute alcohol is also known to affect the hypothalamic-pituitary axis, possibly involving the hormone CRF (corticotrophin releasing factor). This action probably underlies the stress-reducing effects of alcohol