Introduction
Ethanol, aka "alcohol", is perhaps the
most widely consumed drug on Earth. With the exception of its effects on heart
disease, few people would claim it is good for you. But, because of its legality,
omnipresence, and just the fact that it is so much fun, most think very little
of having a few beers or even a few six packs. This includes many bodybuilders.
However, it is far from being a harmless vice,
even in non-alcoholics. It affects numerous neurotransmitters, metabolic processes,
and hormones -- and many of these effects go beyond the time period of intoxication.
These have ramifications, not only for general health, but as you will see,
body composition as well.
This is the first of a two parts series -- We will
first look at the basic science of ethanol, then we will turn to its effects
on body composition in the second installment. We will not be looking at the
effects of chronic ethanol consumption, addiction, and withdrawal, as they are
not relevant to what I consider as my target audience. Suffice it to say, such
a lifestyle is utterly incompatible with getting the most out of one's bodybuilding
efforts.
Biochemistry
Ethanol, in addition to being a drug, is also a
nutrient (1). However, unlike the other nutrients such as carbs, fat and protein,
the body lacks the ability to store ethanol (1) -- It is also the only toxic
macronutrient (1). These two characteristics lead to some important consequences
-- namely, it must be metabolized, and this metabolism take precedence over
all other nutrients (2).
It is metabolized by one of two pathways, depending
on blood levels. The primary is to aldehyde, via alcohol dehydrogenase (ADH)
(3). However, at high levels, what is known as the microsomal ethanol oxidizing
system (MEOS) becomes a significant pathway (4). Both result in conversion to
acetate, then acetyl-CoA -- where it can either a) enter the tricarboxylic acid
cycle and be oxidized into CO2 and water, or b) be stored a fat (1).
Pharmocokinetics
Ethanol is readily bioavailable with oral administration,
however, oral clearance rate and % absorption decrease in the post-prandial
state (i.e. with food) (5), due to the presence of ADH activity in the stomach
(6). The more food in the stomach, the longer the ethanol stays there to be
metabolized before it reaches the bloodstream. The type of food will effect
this, with protein and fat have the greater effect. Fat, due to slowing transport
into the small intestine, protein, probably through direct binding with the
ethanol molecule (7).
The type of drink can also effect blood alcohol
levels obtained - particularly in the fed state. For instance, after a meal,
a less concentrated drink (such as a beer) will be absorbed more quickly than
a more concentrated one (such as a shot) -- and, in rats, this led to an 80%
higher peak blood alcohol level and 95% higher overall absorption (8). However,
on an empty stomach, the opposite was found, though the magnitude of the difference
was not as strong.
It is also interesting to note that when large
amounts are taken in, absorption can exceed systemic distribution, thus exceptionally
high concentrations can occur in arterial blood, and, therefore, the brain (7).
This is why bonging 6 beers right in a row hits you harder than drinking 8 drinks
over 2 hours.
Despite popular opinion to the contrary, women
do not metabolize ethanol more slowly than men - the opposite is in fact true.
Failure to take into account differences in total body water (i.e. LBM) between
men and women has accounted for much of this confusion (9). But, when normalized
for total body water, women metabolize ethanol 33% faster than men, due to a
proportionally larger liver (10).
Due to limitations of ADH, metabolism of ethanol
follows zero-order, straight line kinetics - meaning it is broken down at a
constant rate (about a drink per hour) rather than having a half-life as most
drugs do (11).
DHT has been shown to decrease breakdown of ethanol
by increasing the breakdown of ADH, thus a good testosterone cycle will increase
susceptibility to intoxication (12).
Aldehyde
Aldehyde, as mentioned, is a product of ethanol
metabolism. In the literature, its presence has generally been found to produce
an aversive response, thus the basis of treatment of alcoholics with disulfiram
(13). It is responsible for the flushing seen in some drinkers, usually Asians
-- this can be reduced with the use of antihistamines (14). However, a few studies
have shown it to be involved in the reinforcement of ethanol intake (15).
Aldehyde is also implicated in ethanol's hepatotoxic
effects (16). The amino acid taurine enhances the metabolism of aldehyde by
activating the hepatic enzyme aldehyde dehydrogenase, thus lowering levels --
though this was with the equivalent of 45 grams for a 200lb person (17), so
who knows if supplementing with reasonable levels would be effective.
Pharmacology
Following oral, intravenous, or intraperitoneal
administration, ethanol produces central nervous system (CNS) effects of a biphasic
nature. Lower concentrations (10-25mM -- 3 to 8 drinks) tend to produce stimulant
effects (euphoria) while higher doses result in CNS depression (anti-anxiety,
sedation) (18).
It was thought for quite some time that ethanol
produce its effects through nonspecific means, by acting as a solvent, or interfering
with lipid membranes (19, 20). In fact, as late as a 1997 drug education class
I took in college, we were informed that it worked by coating the cells rather
than interacting with specific receptors like all other drugs. This view has
recently fallen out of favor for several reasons that I won't go into detail
on, and it is now considered to exert its effects through binding to proteins
on specific receptors (21). It is widely held that no specific ethanol receptor
exists, though one prominent researcher suggests that the evidence suggests
we should be moving toward the concept of a specific ethanol receptor (22).
The exact mechanism behind its subjective effects
are still not completely understood, and involve multiple neurotransmitter systems
and ion channels with many studies reporting effects that completely contradict
other ones, and all of this is further complicated by the fact that ethanol
seems to preferentially affect certain subtypes of the various receptors. An
exhaustive presentation is best suited for a 500 page book, thus I have weeded
through and analyzed the research in order to give what I consider the best
overall generalization about its effects on the various systems.
Dopamine
Levels of the central neurotransmitter dopamine
have been consistently shown to be increased by ethanol (23,24), and it is considered
as the primary mediator of the reinforcing effects of all drugs of abuse (25).
It is also involved in behavioral reinforcement in general. Of particular importance
is the mesolimbic dopamine system, which is regulated by neurons in the Ventral
Tagamental Area (VTA) and Nucleus Accumbens (NAC) (26).
Alcohol-preferring rats have been shown to have
lower basal mesolimbic dopaminergic activation and innervation than non-preffering
rats (27) -- as well as altered serotonin, GABA, and opioid activity, all of
which are major modulators of the mesolimbic dopamine system and likely contribute
to the hypofunctioning of this area (27, 28). Acute administration of ethanol
increases extracellular dopamine levels in the NAC as a result of increased
firing of dopamine neurons in the VTA, thus bringing mesolimbic activity toward
normal (29). Thus, ethanol intake is merely representing self-medication --
bringing about behavioral activation (thought analogous to euphoria in humans)
and decreased anxiety in alcohol-preffering rats, while non-preferring rats,
whose dopamine system is not faulty, tend to just become sedated (27).
Opioid
Ethanol has been found to increase brain levels
of the endogenous opioid beta-endorphin (31), and it is likely that the opioid
system mediates a large part of its effects on dopamine levels, by removing
GABA mediated inhibition of dopamine neuron firing (32).
It has been found that alcoholics have lower basal
levels of endogenous opioids than non-alcoholics, and when ethanol is consumed
these levels increase to a level higher than those reached by non-alcoholics
with ethanol consumption (33). Opiod receptor antagonists have been found to
inhibit the reinforcing effects of ethanol in animals and the euphoric effect
in humans (34). One of these, nalaxone, is considered a very promising drug
in the fight against ethanol addiction.
However, if I may opine for a moment, I would like
to point out that opioids are the brain's happy hormones, so alcoholics are
self medicating to bring themselves happiness that the biochemistry of their
brain withholds from them, so a drug that keeps someone from drinking by making
it ineffective at making them happy seems a piss poor approach to me. But, of
course, they would never allow a long-acting morphine for such purposes, because,
heaven forbid, someone might want a little more happiness than The Man deems
appropriate and thus might "abuse" it.
NMDA
The NMDA receptor is one of three types of glutamate
receptors -- the body's primary excitatory neurotransmitter. It is named for
n-Methyl-d-Aspartate, its synthetic, high-affinity ligand (35). Ethanol has
been found to block the action of this receptor (36). The likely mechanism is
by preventing glutamate's removal of a magnesium ion which blocks calcium influx
into the cell (37). This decreases the excitation of the cell, which, along
with increased inhibition via GABA, results in the sedative-depressant effects
of ethanol, particularly at higher doses.
This blockade leads to upregulation of glutamate
receptors (38), which leads to hyperexcitability of the cell when ethanol is
no longer present -- this is one of the mechanisms responsible for ethanol induced
neurotoxicity seen with withdrawal (39). It has also been postulated that the
end of each drinking episode represents a mini-withdrawal complete with the
aforementioned excitotoxicity (40). Because magnesium is the natural antagonist
for the receptor (41), it would probably not be a bad idea to take 400-800 mg
before bed after a night of drinking. Zinc, and the amino acid taurine may be
as well (42,43).
By the way, magnesium and zinc's antagonism of
the NMDA receptor may account for ZMA's positive effects on sleep. Unfortunately,
it is disruption of the NMDA receptor that leads to the decrease in REM sleep
caused by alcohol (43b).
The NMDA receptor complex is also implicated in
memory loss and blackouts from ethanol (35) -- This is due to its effects on
long-term potentiation (LTP). We will address this in more detail later.
GABA
Another very important system is the gamma-aminobutyric
acid (GABA) system -- the body's primary inhibitory pathway (44). Ethanol potentiates
GABA's activity at its receptor (45). It likely has a biphasic effect on behavior,
with lower doses inhibiting inhibitory GABA interneurons on dopamine receptors
in the VTA -- thus causing dopamine induced stimulation and euphoria, and higher
doses producing widespread inhibition of CNS activity, thus overriding the stimulant
effects (46, 47). This is likely one of the major mechanisms through which it
produces its sedative-hypnotic and anxiolytic actions.
Serotonin
Ethanol also has significant effects on serotonin
(5-HT), though it is not as well characterized as the afore mentioned ones.
Ethanol has a biphasic effect on serotonin, first raising levels, then lowering
them (48).
5-HT2 agonists, as well as serotonin reuptake inhibitors,
have been found to substitute for ethanol in drug discrimination tests (49,
50). 5HT3 activity is probably responsible for the nausea with excessive consumption
(51). It is also likely to partially account for increased dopamine release
as antagonists have been shown to block ethanol induced dopamine release (52).
Ethanol administration eventually results in depressed
5-HT levels, and thus activity, due to increased peripheral metabolism of its
precursor, l-tryptophan (53). Low levels of 5-HT are associated with increased
aggression (53), and it is also quite likely that subsequent drinking episodes
(and their accompanying initial increase in 5-HT levels) represent self-medication,
to be followed by a fall in levels and repeat of the cycle. It seems possible
that lowered 5-HT levels could contribute to the malaise of a next-day hangover,
so the use of 50mg of 5-HTP upon waking might not be a bad idea.
Acetylcholine
The cholinergic system is yet another target for
the actions of ethanol (54). It has been found to act as a CO-agonist with acetylcholine
at the nicotinic acetylcholine receptors, as well as to potentiate the effect
of nicotine at this receptor, both of which ultimately results in an increase
in mesolimbic dopamine (55). This interaction accounts quite nicely for the
fact that 90% of ethanol addicts are also nicotine addicts (56).
Cannabinoid
There is also likely some interaction by ethanol
with the endocannabinoid system. They are somewhat similar in their effects
in that both produce euphoria and stimulation at low doses and CNS depression
at high doses (57). Cross-tolerance between the effects of THC and ethanol have
been shown in rats (58), and down regulation of the CB1 subtype of cannabinoid
receptors has been reported in rats chronically exposed to ethanol (59).
N-arichidonyl-ethanolamide (AnNH) is a naturally
occurring derivative of the long-chain fatty acid, arachidonic acid, which has
been found to bind to the CB1 cannabinoid receptor and to mimic the effects
of THC (60). Ethanol increases the formation of AnNH from arachidonic acid.
The administration of a CB1 antagonist has been
shown to limit ethanol consumption, suggesting that it might be involved in
ethanol's reinforcement (62).
Catecholamines
Ethanol consumption increases central and peripheral
levels of epinephrine (E) and norepinephrine (NE), which contributes to the
stimulatory affects of ethanol, particularly in the ascending arm of the blood
alcohol curve (63, 64). Brain levels of norepinephrine have been shown to increase
up to three-fold (64). These elevations occur primarily due to increased release
and decreased clearance, rather than increases in synthesis (65). A consequence
of this is eventual depletion of E and NE stores -- to as low as 8% and 20%
in the adrenals after 4 days of ethanol intoxication (66). This fall likely
contributes to the CNS depression that occurs with prolonged drinking.
Aggression
There exists a real and significant relationship
between ethanol and aggression (67), which might be of particular importance
to bodybuilders who are supplementing with exogenous androgens or an EC stack,
reading T-Mag on a regular basis, or any other things which could already be
facilitating aggressive behavior.
The possible mechanisms by which it does this are
several. As an anxiolytic, it can reduce fear of retaliation and consequences
of behaviors, as a psychomotor stimulant, it can increase sensation-seeking
behavior, and as an analgesic, it can reduce the perception of consequences
of painful stimuli (68).
Another interesting possibility, is that ethanol
disrupts executive cognitive functioning (ECF) (68). ECF encompasses higher
order mental abilities such as abstract reasoning, attention, planning, self-monitoring,
and the ability to adapt future behavior based on feedback from the outside
world - basically ECF is the ability to use the above to consciously self-regulate
goal directed behavior (69).
ECF is governed by the prefrontal cortex (70),
and patients with lesions in this area have been noted to have decreased regulation
of social behavior, including a "disinhibition syndrome" characterized
by impulsivity, socially inappropriate behavior, and aggression (71, 72) - sound
at all familiar? :) Lower scores on tests of ECF processes, such as the ability
to inhibit aggression to obtain a monetary reward, have been reported for both
prefrontal cortex lesioned patients and those intoxicated with ethanol (73).
It should also be noted that it is on the ascending limb of the blood ethanol
curve - i.e. when blood ethanol levels are increasing - when effects on ECF
are particularly apparent (68).
The neurotransmitter, serotonin, has been implicated
in this ethanol induced aggression as well. Decreases in serotonin levels, as
well as 5-HT receptors, have been correlated with aggressive behavior (53).
Acute ethanol consumption decreases the availability of the 5-HT precursor l-tryptophan
to the brain (53). So, it might not be a bad idea to take 25-50mg of 5-HTP if
you are prone to aggressive behavior when drinking.
Neurotoxicity
Alcohol is neuorotoxic, and this toxicity is likely
mediated by several factors. Fatty acid ethyl esters are a toxic byproduct of
fatty acids and ethanol (74) which increase mitochondrial uncoupling and disrupt
lipids of cell membranes (75) -- both l-carnitine and acetyl-l-carnitine in
doses of 50mg/kg have been shown to decrease formation of FAEE by 3 to 6 fold,
with ALC being particularly effective (75).
There is also strong evidence that ethanol induces
oxidative damage -- in the form of increases free-radicals and indirect markers
of oxidative damage such as lipid peroxides and protein carbonyl (76), thus
the use of antioxidants is recommended -- Grape seed extract, resveratrol, SAMe,
ALC, vitamin E, and selenium have all been shown effective (77, 78, 79, 80).
As mentioned previously, NMDA modulated excitotoxicity is another mechanism.
Hepatotoxicity will not be reviewed as it is not
a real concern for non-alcoholics, and alcoholics are not the intended audience
of this article. Though, I will note that the notion that a single episode of
concomitant Tylenol and ethanol use causing permanent liver damage has no basis
in fact (81).
Memory
The NMDA receptor complex is implicated in memory
loss and blackouts from ethanol. This is due to its suppression of long-term
potentiation (LTP) in the hippocampus (35). LTP is a sustained increase in synaptic
efficacy following brief intense stimulation of presynaptic inputs (82) - basically,
it is a physiological change by which memories are formed.
NMDA activation is required for the induction,
but not sustaining of LTP (83), and as mentioned, ethanol results in the blockade
of NMDA receptor transmission. Indeed, ethanol has been directly shown to inhibit
LTP in concentrations as low as 5mM (equivalent to 1-2 drinks) (84).
This effect is very much dose dependent (as well
as exhibiting interindividual differences and tending to be related to rapidly
rising blood ethanol levels) and exists as a continuum, with lower concentrations
producing minor loss and concentrations between 50-100mM (20+ drinks) producing
so-called "blackouts" (85).
Contrary to popular notion, the occurrence of more
frequent blackouts is not a predictor of subsequent alcoholism (86). Blackouts
and short-term memory deficits have been found to be related (87), so if you
want to test whether your drunken friend will experience a blackout the next
day, ask him about a conversation 5 minutes earlier, and if he does not remember
it at all, you will know that he will.
GABA (88), dopamine (89), and serotonin (90)are
also likely to be involved in ethanol induced memory disruption, though the
data for both is scarce at present. With serotonin, this is likely due to decreased
availability of tryptophan and has been shown to be reversible with an SSRI.
Thus, 25-50mg of 5-HTP is again recommended.
Questions and comments on this article can be sent
to ParDeus@avantlabs.com
Be Sure To Check Out Other Chemically Correct Articles:
References
1. Prentice AM. Alcohol and obesity. Int J Obes
Relat Metab Disord 1995 Nov;19 Suppl 5:S44-50
2. Shelmet JJ, Reichard GA, Skutches CL, Hoeldtke
RD, Owen OE, Boden G. Ethanol causes acute inhibition of carbohydrate, fat,
and protein oxidation and insulin resistance. J Clin Invest 1988 Apr;81(4):1137-45
3. Carpenter TM. The metabolism of alcohol: A review.
Quart j Stud alcohol 1940 1:201-226
4. Pirola RC, Lieber CS. Hypothesis: energy wastage
in alcoholism and drug abuse: possible role of hepatic microsomal enzymes.Am
J Clin Nutr 1976 Jan;29(1):90-3
5. Jones AW, Jonsson KA. Food-induced lowering
of blood-ethanol profiles and increased rate of elimination immediately after
a meal. J Forensic Sci 1994 Jul;39(4):1084-93
6. Hernandez-Munoz R, Caballeria J, Baraona E,
Uppal R, Greenstein R, Lieber CS. Human gastric alcohol dehydrogenase: its inhibition
by H2-receptor antagonists, and its effect on the bioavailability of ethanol.
Alcohol Clin Exp Res 1990 Dec;14(6):946-50
7. Gentry RT. Effect of food on the pharmacokinetics
of alcohol absorption. Alcohol Clin Exp Res 2000 Apr;24(4):403-4
8. Roine R. Interaction of prandial state and beverage
concentration on alcohol absorption. Alcohol Clin Exp Res 2000 Apr;24(4):411-2
9. Kalant H. Effects of food and body composition
on blood alcohol curves. Alcohol Clin Exp Res 2000 Apr;24(4):413-4
10. Thomasson H. Alcohol elimination: faster in
women? Alcohol Clin Exp Res 2000 Apr;24(4):419-20
11. Lundquist F, Wolthers H. The kinetics of alcohol
elimination in man. Acta Pharmacol Toxicol 1958; 14:265-289
12. Vaubourdolle M, Guechot J, Chazouilleres O,
Poupon RE, Giboudeau J. Effect of dihydrotestosterone on the rate of ethanol
elimination in healthy men. Alcohol Clin Exp Res 1991 Mar;15(2):238-40
13. Johnsen J, Stowell A, Morland J. Clinical responses
in relation to blood acetaldehyde levels. Pharmacol Toxicol 1992 Jan;70(1):41-5
14. Alcohol-histamine interactions. Zimatkin SM,
Anichtchik OV. Alcohol Alcohol 1999 Mar-Apr;34(2):141-7
15. Takayama S, Uyeno ET. Intravenous self-administration
of ethanol and acetaldehyde by rats.Yakubutsu Seishin Kodo 1985 Dec;5(4):329-34
16. Lieber CS. Hepatic, metabolic and toxic effects
of ethanol: 1991 update. Alcohol Clin Exp Res 1991 Aug;15(4):573-92
17. Alcohol Alcohol 2001 Jan-Feb;36(1):39-43 Taurine
modulates catalase, aldehyde dehydrogenase, and ethanol elimination rates in
rat brain. Ward RJ, Kest W, Bruyeer P, Lallemand F, De Witte P.
18. Little HJ. The contribution of electrophysiology
to knowledge of the acute and chronic effects of ethanol. Pharmacol Ther 1999
Dec;84(3):333-53
19. Goldstein DB. The effects of drugs on membrane
fluidity.Annu Rev Pharmacol Toxicol 1984;24:43-64
20. Seeman P.Pharmacol Rev The membrane actions
of anesthetics and tranquilizers. 1972 Dec;24(4):583-655
21. Peoples RW, Li C, Weight FF. Lipid vs protein
theories of alcohol action in the nervous system. Annu Rev Pharmacol Toxicol
1996;36:185-201
22. Harris RA. Ethanol actions on multiple ion
channels: which are important? Alcohol Clin Exp Res 1999 Oct;23(10):1563-70
23. Little HJ. Mechanisms that may underlie the
behavioural effects of ethanol. Prog Neurobiol 1991;36(3):171-94
24. Samson HH, Tolliver GA, Haraguchi M, Hodge
CW. Alcohol self-administration: role of mesolimbic dopamine. Ann N Y Acad Sci
1992 Jun 28;654:242-53
25. Manley LD, Kuczenski R, Segal DS, Young SJ,
Groves PM. Effects of frequency and pattern of medial forebrain bundle stimulation
on caudate dialysate dopamine and serotonin. J Neurochem 1992 Apr;58(4):1491-8
Erickson CK. Review of neurotransmitters and their
role in alcoholism treatment.Alcohol Alcohol Suppl 1996 Mar;1:5-11
26. McBride WJ, Murphy JM, Ikemoto S. Localization
of brain reinforcement mechanisms: intracranial self-administration and intracranial
place-conditioning studies. Behav Brain Res 1999 Jun;101(2):129-52
27. McBride WJ, Li TK. Animal models of alcoholism:
neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol
1998;12(4):339-69
28. Zhou FC, Pu CF, Murphy J, Lumeng L, Li TK.
Serotonergic neurons in the alcohol preferring rats. Alcohol 1994 Sep-Oct;11(5):397-403
29. Li TK. Pharmacogenetics of responses to alcohol
and genes that influence alcohol drinking. J Stud Alcohol 2000 Jan;61(1):5-12
31. de Waele JP, Kiianmaa K, Gianoulakis C. Spontaneous
and ethanol-stimulated in vitro release of beta-endorphin by the hypothalamus
of AA and ANA rats. Alcohol Clin Exp Res 1994 Dec;18(6):1468-73
32. Gianoulakis C. Implications of endogenous opioids
and dopamine in alcoholism: human and basic science studies. Alcohol Alcohol
Suppl 1996 Mar;1:33-42
33. Johnson SW, North RA. Opioids excite dopamine
neurons by hyperpolarization of local interneurons. J Neurosci 1992 Feb;12(2):483-8
34. Altshuler HL, Phillips PE, Feinhandler DA.
Alteration of ethanol self-administration by naltrexone. Life Sci 1980 Mar 3;26(9):679-88
35. Woodward JJ. Ethanol and NMDA receptor signaling.
Crit Rev Neurobiol 2000;14(1):69-89
36. Dildy JE, Leslie SW. Ethanol inhibits NMDA-induced
increases in free intracellular Ca2+ in dissociated brain cells. Brain Res 1989
Oct 16;499(2):383-7
37. Collingridge GL, Bliss TV. Memories of NMDA
receptors and LTP.Trends Neurosci 1995 Feb;18(2):54-6
38. Gulya K, Grant KA, Valverius P, Hoffman PL,
Tabakoff B. Brain regional specificity and time-course of changes in the NMDA
receptor-ionophore complex during ethanol withdrawal. Brain Res 1991 Apr 26;547(1):129-34
39. Iorio KR, Tabakoff B, Hoffman PL. Glutamate-induced
neurotoxicity is increased in cerebellar granule cells exposed chronically to
ethanol. Eur J Pharmacol 1993 Aug 2;248(2):209-12
40. Nutt D. Alcohol and the brain. Pharmacological
insights for psychiatrists. Br J Psychiatry 1999 Aug;175:114-9
41. Chandler LJ, Guzman NJ, Sumners C, Crews FT.
J Pharmacol Exp Ther 1994 Oct;271(1):67-75 Magnesium and zinc potentiate ethanol
inhibition of N-methyl-D-aspartate-stimulated nitric oxide synthase in cortical
neurons.
42. Westbrook GL, Mayer ML. Micromolar concentrations
of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 1987
Aug 13-19;328(6131):640-3
43. Kurachi M, Yoshihara K, Aihara H. Effect of
taurine on depolarizations induced by L-glutamate and other excitatory amino
acids in the isolated spinal cord of the frog. Jpn J Pharmacol 1983 Dec;33(6):1247-54
43b. Prospero-Garcia O, Criado JR, Henriksen SJ.
Pharmacology of ethanol and glutamate antagonists on rodent sleep: a comparative
study.Pharmacol Biochem Behav 1994 Oct;49(2):413-6
44. Meldrum B. Pharmacology of GABA. Clin Neuropharmacol
1982;5(3):293-316
45. Suzdak PD, Schwartz RD, Skolnick P, Paul SM.
Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport
in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A 1986 Jun;83(11):4071-5
46. Kalivas PW, Duffy P, Eberhardt H. Modulation
of A10 dopamine neurons by gamma-aminobutyric acid agonists. J Pharmacol Exp
Ther 1990 May;253(2):858-66
47. Grobin AC, Matthews DB, Devaud LL, Morrow AL.
The role of GABA(A) receptors in the acute and chronic effects of ethanol. Psychopharmacology
(Berl) 1998 Sep;139(1-2):2-19
48. LeMarquand D, Pihl RO, Benkelfat C. Serotonin
and alcohol intake, abuse, and dependence: clinical evidence. Biol Psychiatry
1994 Sep 1;36(5):326-37
49. Maurel S, Schreiber R, De Vry J. Substitution
of the selective serotonin reuptake inhibitors fluoxetine and paroxetine for
the discriminative stimulus effects of ethanol in rats. Psychopharmacology (Berl)
1997 Apr;130(4):404-6
50. Signs SA, Schechter MD. The role of dopamine
and serotonin receptors in the mediation of the ethanol interoceptive cue. Pharmacol
Biochem Behav 1988 May;30(1):55-64
51. Wilde MI, Markham A. Ondansetron. A review
of its pharmacology and preliminary clinical findings in novel applications.
Drugs 1996 Nov;52(5):773-94
52. Carboni E, Acquas E, Frau R, Di Chiara G. Differential
inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine
release. Eur J Pharmacol 1989 May 30;164(3):515-9
53. Badawy AA, Morgan CJ, Lovett JW, Bradley DM,
Thomas R. Decrease in circulating tryptophan availability to the brain after
acute ethanol consumption by normal volunteers: implications for alcohol-induced
aggressive behaviour and depression. Pharmacopsychiatry 1995 Oct;28 Suppl 2:93-7
54. Narahashi T, Aistrup GL, Marszalec W, Nagata
K. Neuronal nicotinic acetylcholine receptors: a new target site of ethanol.
Neurochem Int 1999 Aug;35(2):131-41
55. Soderpalm B, Ericson M, Olausson P, Blomqvist
O, Engel JA. Nicotinic mechanisms involved in the dopamine activating and reinforcing
properties of ethanol. Behav Brain Res 2000 Aug;113(1-2):85-96
56. Batel P, Pessione F, Maitre C, Rueff B. Addiction
1995 Jul;90(7):977-80 Relationship between alcohol and tobacco dependencies
among alcoholics who smoke.
57. Hollister LE, Gillespie HK. Mood and mental
function alterations. Marihuana, ethanol, and dextroamphetamine. Arch Gen Psychiatry
1970 Sep;23(3):199-203
58. Newman LM, Lutz MP, Gould MH, Domino EF. 9
-Tetrahydrocannabinol and ethyl alcohol: evidence for cross-tolerance in the
rat. Science 1972 Mar 3;175(25):1022-3
59. Basavarajappa BS, Cooper TB, Hungund BL. Chronic
ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic
plasma membrane. Brain Res 1998 May 18;793(1-2):212-8
60. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson
LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and
structure of a brain constituent that binds to the cannabinoid receptor. Science
1992 Dec 18;258(5090):1946-9
61. Basavarajappa BS, Hungund BL. Chronic ethanol
increases the cannabinoid receptor agonist anandamide and its precursor N-arachidonoylphosphatidylethanolamine
in SK-N-SH cells. J Neurochem 1999 Feb;72(2):522-8
62. Arnone M, Maruani J, Chaperon F, Thiebot MH,
Poncelet M, Soubrie P, Le Fur G. Selective inhibition of sucrose and ethanol
intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology
(Berl) 1997 Jul;132(1):104-6
63. Pohorecky LA. Influence of alcohol on peripheral
neurotransmitter function. Fed Proc 1982 Jun;41(8):2452-5
64. Wang YL, Wei JW, Sun AY. Effects of ethanol
on brain monoamine content of spontaneously hypertensive rats (SHR). Neurochem
Res 1993 Dec;18(12):1293-7
65. Howes LG, MacGilchrist A, Hawksby C, Sumner
D, Reid JL. Plasma [3H]-noradrenaline kinetics and blood pressure following
regular, moderate ethanol consumption. Br J Clin Pharmacol 1986 Nov;22(5):521-6
66. Adams MA, Hirst M. Adrenal and urinary catecholamines
during and after severe ethanol intoxication in rats: a profile of changes.
Pharmacol Biochem Behav 1984 Jul;21(1):125-31
67. Bushman BJ, Cooper HM. Effects of alcohol on
human aggression: an integrative research review. Psychol Bull 1990 May;107(3):341-54
68. Hoaken PN, Giancola PR, Pihl RO. Executive
cognitive functions as mediators of alcohol-related aggression. Alcohol Alcohol
1998 Jan-Feb;33(1):47-54
69. Stuss DT, Benson DF. Neuropsychological studies
of the frontal lobes. Psychol Bull 1984 Jan;95(1):3-28
70. Peterson JB, Rothfleisch J, Zelazo PD, Pihl
RO. Acute alcohol intoxication and cognitive functioning. J Stud Alcohol 1990
Mar;51(2):114-22
71. Alcohol Clin Exp Res 1995 Feb;19(1):130-4 Related
Articles, Books, LinkOut Alcohol-related aggression in males and females: effects
of blood alcohol concentration, subjective intoxication, personality, and provocation.
Giancola PR, Zeichner A.
72. Heinrichs RW. Frontal cerebral lesions and
violent incidents in chronic neuropsychiatric patients. Biol Psychiatry 1989
Jan 15;25(2):174-8
73. Hoaken PN, Assaad JM, Pihl RO. Cognitive functioning
and the inhibition of alcohol-induced aggression. J Stud Alcohol 1998 Sep;59(5):599-607
74. Saghir M, Werner J, Laposata M. Rapid in vivo
hydrolysis of fatty acid ethyl esters, toxic nonoxidative ethanol metabolites.
Am J Physiol 1997 Jul;273(1 Pt 1):G184-90
75. Calabrese V, Scapagnini G, Catalano C, Dinotta
F, Bates TE, Calvani M, Stella AM. Effects of acetyl-L-carnitine on the formation
of fatty acid ethyl esters in brain and peripheral organs after short-term ethanol
administration in rat. Neurochem Res 2001 Feb;26(2):167-74
76. Mantle D, Preedy VR. Free radicals as mediators
of alcohol toxicity. Adverse Drug React Toxicol Rev 1999 Nov;18(4):235-52
77. J Nutr 1973 Apr;103(4):536-42 Related Articles,
Books Nutritional interrelationships among vitamin E, selenium, antioxidants
and ethyl alcohol in the rat. Levander OA, Morris VC, Higgs DJ, Varma RN.
78. Sun AY, Sun GY. Ethanol and oxidative mechanisms
in the brain. J Biomed Sci 2001 Jan-Feb;8(1):37-43
79. Lieber CS. ALCOHOL: its metabolism and interaction
with nutrients. Annu Rev Nutr 2000;20:395-430
80. Cha YS, Sachan DS. Acetylcarnitine-mediated
inhibition of ethanol oxidation in hepatocytes. Alcohol 1995 May-Jun;12(3):289-94
81. Prescott LF. Paracetamol, alcohol and the liver.
Br J Clin Pharmacol 2000 Apr;49(4):291-301
82. Givens B, McMahon K. Ethanol suppresses the
induction of long-term potentiation in vivo Brain Res 1995 Aug 7;688(1-2):27-33
83. Woodward JJ. Ethanol and NMDA receptor signaling.
Crit Rev Neurobiol 2000;14(1):69-89
84. Blitzer RD, Gil O, Landau EM. Long-term potentiation
in rat hippocampus is inhibited by low concentrations of ethanol. Brain Res
1990 Dec 24;537(1-2):203-8
85. Melia KR, Ryabinin AE, Corodimas KP, Wilson
MC, Ledoux JE. Hippocampal-dependent learning and experience-dependent activation
of the hippocampus are preferentially disrupted by ethanol. Neuroscience 1996
Sep;74(2):313-22
86. Melchior CL, Ritzmann RF. Neurosteroids block
the memory-impairing effects of ethanol in mice. Pharmacol Biochem Behav 1996
Jan;53(1):51-6
87. Goodwin DW, Hill SY Short-term memory and the
alcoholic blackout.Ann N Y Acad Sci 1973 Apr 30;215:195-9
88. Goodwin DW. Alcoholic blackout and state-dependent
learning. Fed Proc 1974 Jul;33(7):1833-5
89. White AM, Matthews DB, Best PJ. Ethanol, memory,
and hippocampal function: a review of recent findings. Hippocampus 2000;10(1):88-93
90. Lau AH, Frye GD. Acute and chronic actions
of ethanol on CA1 hippocampal responses to serotonin. Brain Res 1996 Aug 26;731(1-2):12-20
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