Jane behaving badly
New Scientist, 27 November 1999
ALISON MOTLUKDear Ms Tipple,Your
behaviour last night at the office millennium party was appalling.
Within an hour of arriving, you were singing bawdy songs and shouting
obscenities at your colleagues. Then, minutes later, you began to
disrobe. As if that weren't bad enough, you astonished us all when you
attempted to kiss the Chairmam, Mr Monk. He can be considered lucky,
however, that he was out of range when, soon after, you began to vomit.
Ms Stern from accounts cannot count herself so lucky. I can tell you,
we were all much relieved when you passed out and were removed to the
hospital for observation. Can you please explain how this happened?
Jane Tipple. If it weren't for the throbbing headache keeping her
tucked up in bed and the fact that many of the sorry details of the
previous evening never even made it into her long-term memory, she
could probably explain a good deal of what happened. The raw facts are
simple. She drank too much, too quickly. And her brain became utterly
Getting drunk is not as straightforward as it
appears. During the course of a binge, your brain becomes a veritable
fairground House of Horror-with alcohol at the controls. Neurons
flicker on and off, your metabolic rate rises and falls and brain
signals get mixed up. As your blood alcohol levels rise, you are slowly
drawn upwards along a track of excitement, with alcohol coaxing out the
singing, joke-telling, gregarious you.
But as the booze levels
start to peak, so do you. It's all downhill from there. Now the demon
drink plays its best tricks, slurring your speech, fumbling your
movements and encouraging behaviour you'd regret for the rest of your
life-if only you could remember it. Out of control, you just take the
ride as it comes-sniggering, stumbling, spinning and spewing on cue.
it was for Jane. Arriving at the party straight from work, she took her
first drink, a rum and Coke, just to loosen up. It worked. But although
she may have felt she was relaxing, at this early stage her brain was
in fact revving up.
Stimulation is the first effect of drinking,
and it occurs while blood alcohol levels remain relatively low, says
Boris Tabakoff, a pharmacologist at the University of Colorado Medical
School in Denver. The alcohol concentration in Jane's blood was still
hovering around a modest 25 milligrams per 100 millilitres (see
Diagram). At that level, says Tabakoff, alcohol sensitises one of the
brain's major excitatory message pathways, the N -methyl-D-aspartate
(NMDA) system, making certain NMDA receptors more readily activated by
the brain's main neurotransmitter glutamate. Some of the most
sensitised brain regions are the thinking, remembering and
pleasure-seeking parts-the cortex, hippocampus and nucleus accumbens,
Ratcheting up brain activity reduces inhibitions.
And not just in humans: rats given small doses of alcohol tend to move
around and explore their environments more. In fact anyone who has had
a glass of Chardonnay to calm their nerves at lunch or an after-work
pint with the boss knows this warm, confident feeling. At first, it
helped Jane to get over the anxiety of rubbing shoulders with her more
spirited colleagues. Slowly, it brought out her more vivacious side.
snapshot of her brain at this point would probably show increased
metabolism in the regions associated with movement, such as the
nigrostriatal pathway. This could help explain how she became
uncharacteristically animated as she started telling raucous jokes and
swearing. Linda Porrino, a neuroscientist at Wake Forest University
School of Medicine in Winston-Salem, North Carolina, has examined brain
slices from rats given the equivalent of one drink-what she calls a
"party dose". She found that motor areas and particularly the reward
circuitry were all lit up. It's the effects of these low doses of
alcohol that we seem to like, she says.
Jane was no exception.
She reached for her second and third drinks-two shots of tequila-and
quickly downed them. As she and a colleague linked arms and began
belting out songs, the level of alcohol in her blood was rising, edging
quickly past 50 mg per 100 ml and onwards to break the British legal
driving limit of 80.
Onwards and upwards
flushed and euphoric. She thought the evening could only get better. If
electrodes had been glued to her head at that moment, we'd have found
an increase in alpha brain waves-the slow, rhythmic pattern seen on
electroencephalographs (EEGs) which usually appears when we're relaxed.
According to a study of 18 healthy men by Scott Lucas of Harvard
Medical School in Boston and his colleagues, euphoria correlates well
with transient boosts in alpha waves (Pharmacology Biochemistry and
Behavior, vol 25, p 889).
Another glimpse into her brain might
have shown extra blood flowing to the front, to the prefrontal cortex,
and to the right side, the right temporal cortex. This is what Nora
Volkow of the Brookhaven National Laboratory in New York found when she
used positron emission tomography (PET) to peek into the brains of
drunks. Increased blood flow to these areas might account for Jane's
heightened mood. But no PET scan can explain Jane's ill-fated attempt
to seduce a balding bachelor.
The brain has a complex "biphasic"
relationship with alcohol, and if Jane's first hour was a titillating
ride onwards and upwards, she was now poised to plummet. Now, with her
blood awash with alcohol, the very NMDA receptors that helped to perk
her up earlier in the evening when she'd drunk only a little were
refusing to respond. For most people, the turning point seems to be
three or four drinks, says Tabakoff, who has looked at the effect of
alcohol on NMDA receptors in humans, rodents and cell cultures (Neuron,
vol 16, p 909).
Not only was Jane's NMDA excitement waning, but
another set of pathways in her brain, known as the gamma-aminobutyric
acid system, or GABA, was coming online. Unfortunately for Jane, who
wanted to keep on rocking, GABA is one of the major inhibitory systems
in the brain. It stops neurons from firing and dulls activity. Indeed,
this is the very system activated by benzodiazepines such as Valium.
From here on, rather than winding a person up, alcohol begins to act
more as a sedative. "Now they're feeling more relaxed not simply
because they've become less inhibited in behaviour," says Tabakoff.
"They really are more relaxed." Jane was feeling very relaxed indeed
and, while licking her fourth drink, a beer, off a plate, she began to
take her clothes off.
By this time, Jane had consumed what
Porrino calls the "spending too much time at the bar" dose and new
areas of her brain were being affected. Porrino has compared the
effects of the equivalent of one drink and four drinks on rats'
brains-and the two are completely different. While low doses increase
neural activity, particularly in motor and reward areas, high doses
slow the hippocampus, which processes memory, and the thalamus, which
helps to deal with sensory and motor information. "Different alcohol
doses distinctly affected different brain regions rather than acted on
a single system in a dose-dependent way," she says in the journal
Alcohol Health & Research World (vol 19, p 300).
finished her fifth drink, whatever it was, Jane's mouth had forgotten
how to speak, let alone sing, and standing seemed like too much effort,
so she slumped into a corner. Volkow's work, another PET study,
suggests this could be because alcohol reduces blood flow to the
cerebellum, a structure at the back of the brain that is involved in
motor coordination and posture. Volkow asked volunteers to drink the
equivalent of three shots of vodka, then scanned their brains once the
alcohol had been absorbed. "The cerebellum may be one of the brain
areas most sensitive to alcohol," she says (Alcohol Health &
Research World, vol 19, p 296).
Volkow also looked at glucose
metabolism, asking 10 healthy people to drink the equivalent of three
small drinks to boost their blood alcohol levels to about 80 mg per 100
ml. To her surprise, she found that the drunken brain consumed 25 per
cent less glucose than the sober one. "I am very intrigued by this,"
she says. "If neurons are not consuming glucose, they won't be working
properly. That could account for many of the impairments."
when she looked at the brain region by region, it became clear what was
behind some of the specific symptoms of intoxication. She found that
the greatest decrease in metabolism occurred at the back of the brain,
in the occipital lobe, where glucose consumption was down by 29 per
cent. This is where the visual cortex is and may help explain the
blurry vision that accompanies late-stage drunkenness. The second
biggest decrease in glucose uptake, down 27 per cent, was in the
cerebellum. When the volunteers were rated on how they moved and spoke
and recalled, it was found that fine motor skills, speech and memory
were all affected.
Sitting there quietly in the corner, Jane was
overwhelmed with a groggy feeling. She has no recollection of sipping
her sixth drink-a fancy green concoction specially prepared and
delivered to her by a bartender who found her amusing.
person continues to drink to excess, a series of other brain receptors
comes into play, says Tabakoff. "Depending on the dose consumed and the
blood alcohol levels, different receptors are differentially affected,"
he says. These include certain acetylcholine receptors-the same ones
that respond to nicotine-and some receptors for serotonin, a
wide-ranging neurotransmitter that can affect anything from mood and
aggression to sexual motivation and attention.
Tabakoff, there's a great deal of genetic variation in how particular
receptors respond to these higher levels of alcohol. Some individuals
are genetically inclined to pick a fight. Others doze off. This
dichotomy is as true in monkeys and mice as in people, he says. "There
are very different reactions." Jane was the sleepy kind.
seldom get a good night's sleep, however, as alcohol interferes with
normal sleep patterns. Though it causes sedation, alcohol also
suppresses rapid eye movement (REM) sleep-the dream phase-by as much as
20 per cent, says Timothy Roehrs, a sleep researcher at the Henry Ford
Hospital in Detroit, Michigan.
Worse, after you have fallen
asleep, and alcohol has gradually been eliminated from your body, you
can become aroused again and wake up. Roehrs has studied how long it
takes people to fall asleep. He found that drinkers whose blood alcohol
level is rising take longer than controls to drop off, while those
whose blood alcohol is falling take less time. But he also thinks that
alcohol-induced sleepiness and memory loss may be linked.
noticed that people who get drunk and then forget what happened have
memory impairments similar to those suffered by people with sleep
disorders. "What's really interesting is that this is an important
phenomenon in patients who have daytime sleepiness," he says. They can
get to work but can't remember having driven there. Similarly, drunks
can get home from the pub without the faintest recollection of who they
insulted while they were there, how they travelled back-or even who
they brought with them. For her part, Jane doesn't recall vomiting on
Roehrs wanted to examine further the relationship
between sleepiness and memory loss, so he gave volunteers-some under
the influence, some not-16 word pairs to remember. The more they drank,
the fewer word pairs they recalled 30 minutes later. In fact, the
dose-related memory effect was very similar to the dose-related
sedative effect. "More than likely, what has been disturbed was the
transfer of memory to the long term store," he says.
agrees that memory is impaired when a person drinks too much, but, says
Roehrs, there is little consensus on why. His hunch is that the GABA
signals that bring on the sleepiness can interfere with both the early
and late stages of memory formation, known as stimulus registration and
consolidation. He knows that chemicals that mimic GABA can do this
(Alcohol Health & Research World, vol 19, p 130). And he points out
that there are many GABA receptors in the hippocampus, the brain's
memory centre. "This is probably the mechanism by which alcohol has
affected memory loss," he says.
Jane does vaguely remember one
thing towards the end of her evening: as she tried to snooze in the
corner, she had the strong sensation that the room was spinning. This
effect is called "positional alcohol nystagmus"-basically a
booze-induced version of an eye reflex that is normally triggered by
the inner ear's balance organs when they detect head rotation.
Ironically, nystagmus is one way of maintaining clear vision while you
turn your head.
Ken Money, former astronaut, and senior
scientist at the Defence and Civil Institute of Environmental Medicine
in Toronto, looked into the phenomenon while working on space sickness
and the effect of weightlessness on balance. He points out that when
you're drunk and your head is tilted, the nystagmus reflex is induced
by the ear's fluid-filled semicircular canals picking up the effect of
gravity-something they don't normally do as they monitor the head
turning. And it was not at all clear why. "Gravity is not supposed to
act in the semicircular canals," says Money. He found that in some
circumstances, however, the canals do respond to gravity-such as after
a double on an empty stomach.
Alcohol has a lower density than
water, and when you get drunk, that lower density creates a "light
spot" in the inner ear fluid. When you lie down, that light spot allows
a sensor called the cupula to sink, sending a faulty report to the
brain that your head is rotating and that your eyes need to rotate too.
So when you're lying with your right cheek on the dance floor, your
eyeballs are turning slowly to the left, then flicking quickly back to
the right-and therein lies the wooziness. Lie with the other cheek
down, and the world spins the other way. The effect, says Money, peaks
at around an hour and a half after a heavy drinking bout begins-and
revisits you in reverse about 10 hours later.
To prove this,
Money got 10 volunteers to drink deuterium oxide, or heavy water. This
created a "heavy" spot, so the spinning was in the opposite direction
to that induced by alcohol. In cats, he showed that the effects of the
alcohol and the heavy water cancelled each other out (Nature, vol 247,
p 404). Fred Miles of the National Eye Institute in Bethesda, Maryland,
suggests mixing all drinks with heavy water to keep the specific
gravity at one, the same as body fluids, to avoid the post-indulgence
spins. "The problem is," he says, "this makes the cocktails very
Jane spun and edged her way up to the anaesthetic
dose, but was still safely short of the blood alcohol concentration of
500 mg per 100 ml that is considered lethal. At that concentration, the
brain centres that keep you breathing shut down. But Jane was
definitely breathing; her loud snores were reverberating around the