Posted by Ron Hill on December 23, 2004, at 19:23:05
In reply to Re: Other new meds for alcohol cravings » lars1, posted by barbaracat on December 22, 2004, at 17:05:53
> Can anyone point me in the direction of just what happens neurologically from drinking? One hears of its CNS dampening properties and then one hears about the buzz created by dopamine? and then there's the affinity for opiod receptors. What's really going on with alcohol? Why does it make us feel so good?
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> Benzos may be a CNS depressant but they do NOT make me feel like dancing around the room singing sappy songs and then jumping into the sack. Why hasn't anyone figured out a way to duplicate alcohol's enjoyable effects minus the awful day-after ones?http://www.scienceblog.com/community/older/2000/E/200004725.html
Brain steroid a key player in alcohol's effects
CHAPEL HILL -- Scientists at the University of North Carolina School of Medicine may have an answer for one of the biggest questions in the alcohol research field -- how does alcohol exert its effects in the brain?
In a report published in the Journal of Neuroscience March 1, researchers headed by A. Leslie Morrow, PhD, associate professor of psychiatry and pharmacology at UNC-CH discovered that a brain steroid called allopregnanolone is likely an important mediator of alcohol's well-known effects on anxiety and sedation. Morrow's study collaborators include lead-author and graduate student Margaret J. VanDoren, Douglas B. Matthews, PhD, Gregory C. Janis, MA, A. Chistina Grobin, PhD, and Leslie L. Devaud, PhD.
The findings add important new knowledge to the previous work showing that alcohol works on brain cell receptors for the neurotransmitters known as GABA and glutamate.
"It's been known for some time that in addition to having direct effects in the brain on these receptors, alcohol activates the hypothalamic-pituitary-adrenal axis in which nerve signals are converted to hormone signals. And this results in the release of a number of compounds in the brain that could contribute to alcohol's actions," Morrow said.
At the UNC Bowles Center for Alcohol Studies, Morrow's team set their sites on the neuroactive steroid allopreganolone. This is the most potent modulator of GABA-A receptors, which are believed to play a role in many of alcohol's effects.
"And we asked a very simple question: Does ethanol (alcohol) alter levels of this steroid in the brain? And in our studies of laboratory rats, we found that indeed ethanol elevates allopreganolone levels in the brain to pharmacologically active concentrations that have previously been shown to have anti-anxiety and anti-convulsant effects," said Morrow.
The UNC scientist also noted that alcohol's effects on brain concentrations of allopregnanolone are time-dependent. "It takes about 20 minutes for this effect to be observed. And what was interesting is we showed this correlates with the anticonvulsant effects of ethanol, which also take about 20 minutes to be observed."
In addition, Morrow's study team discovered that these temporal findings correlate with the physiological effects of alcohol in the brain. "Ethanol reduces spontaneous neural activity in a number of brain regions but it takes about 15 to 20 minutes for that effect to be observed."
And when the UNC researchers looked at alcohol-induced sleep duration, they found it correlated well with increased brain concentrations of allopregnanolone.
But what would happen if ethanol's ability to increase the steroid's level in the brain was blocked? Would alcohol's electrophysiological and anticonvulsant actions be inhibited as well?
The answer appears to be yes.
In a series of experiments, Morrow and her colleagues turned to a compound called finasteride. This compound blocks an enzyme called 5-alpha-reductase. Finasteride inhibits the formation of allopregnanolone from its precursor progesterone.
"And when we pretreated the animals with finasteride, we inhibited ethanol-induced formation of allopregnanolone by a maximum of 50%," Morrow said.
Following pre-treatment with finasteride, no decrease in spontaneous neural activity due to alcohol was observed in the area of the brain associated with alcohol's sedative-hypnotic effects. Nor were ethanol's anticonvulsant effects observed.
"These findings suggest that allopreganolone plays an important role in the actions of alcohol, at least in the rat," Morrow said.
However, the implications for people are tantalizing.
"This also might be very relevant to our understanding of alcoholism because females have much higher endogenous levels of the compound than males," Morrow said. "And those levels vary across the menstrual cycle and are increased dramatically during pregnancy."
She added: "Females are much less likely to become alcoholics than males statistically. So it's possible that this compound - allopregnanolone - mediates some other effects of alcohol, such as the rewarding effect [in the brain] of ethanol, or it mediates the control mechanism that tells you, 'I've had enough to drink, thank you very much; I feel good.' And since females have much higher levels of this compound in the first place, they might be less likely to drink and less likely to drink as much."
Morrow said research on the role of brain steroids in human subjects is underway.
Funding for the new research came from the National Institute on Alcohol Abuse and Alcoholism.
Note to media: Contact Dr. Morrow at 919-966-7682; email: morrow@med.unc.edu
UNC-CH School of Medicine contacts: Karen Stinneford, 919-966-6047; email: kstinnef@unch.unc.edu
Leslie H. Lang can be contacted at 919-843-9687; email: llang@med.unc.edu
poster:Ron Hill
thread:425696
URL: http://www.dr-bob.org/babble/20041223/msgs/433548.html