Yet more evidence that many drugs cause same addiction?

30 November 2001 16:35 EST
by Apoorva Mandavilli, BioMedNet News

Lines of evidence are converging in support of the popular theory in
addiction research: that a common mechanism links intake of different
kinds of addictive drugs with the orbitofrontal cortex, which is the
seat of compulsive behavior and "go-no-go" decision-making. Fresh
support today comes from researchers at the Brookhaven National
Laboratory (BNL) in New York, who report that like abusers of cocaine
and alcohol, users of the popular drug methamphetamine have fewer
dopamine D2 receptors, and an associated decrease in metabolic activity
of the brain region.
Abstinence can restore the damaged dopamine terminals structurally, they
report in a related study. But motor and cognitive function do notrecover.
"One of the holy grails of addiction research is to uncover what brain
areas are involved in regulating addiction and craving," said Bertha
Madras, professor of psychobiology at Harvard Medical School. "The
orbitofrontal cortex is beginning to emerge as the key region."
The stimulant methamphetamine - also known as "speed" or "crank" -
releases large amounts of dopamine, which is associated with pleasure
and reward, and is also essential for movement. Using positron emission
tomography (PET) and a radiotracers that bind glucose (a marker for
brain metabolism) and dopamine D2 receptors, Nora Volkow and her
colleagues at BNL found that meth-induced depletion of D2 receptors
increasingly disrupts orbitofrontal cortex. The results are published in
the December American Journal of Psychiatry.
Cocaine, heroin and alcohol are all known to disrupt metabolic activity
of the region, so "adding meth to the list of drugs that affect the
region implies that it might be a common mechanism," Madras told
BioMedNet News. Madras says she herself has soon-to-be published data
supporting this hypothesis, but declined to elaborate.
Because of blunted orbitofrontal cortex activity, in drug abusers
"ordinary stimuli are not strong enough to activate the circuits," or
trigger a reward response, said lead investigator Volkow.
Methamphetamine releases an enormous amount of dopamine and triggers all
of its receptors; the only stimulus able to boost orbitofrontal cortex
activity, it becomes irresistible to addicts. Meth users also have
significantly depleted dopamine transporters, reduced cognitive and
motor functions, and perhaps a predisposition to Parkinson's disease or
similar disorders.
In a second study, appearing tomorrow in the Journal of Neuroscience,
Volkow and her colleagues report that prolonged abstinence from the drug
can restore levels of dopamine transporters, but do not significantly
improve cognitive and motor function. "It's very important to have this
information out to the public," said Madras, who called the irreversible
losses "alarming." Most studies rely on post-mortem analysis, and
there's little or no information about irreversible effects of drug use.
There may be several reasons why structural repair does not presage
cognitive recovery: Meth abuse also damages serotonin and glutamate
systems, for example, and meth users are prone to mild depression. PET
scanning may also not pick up changes like neuroplasticity and response
to stimulus, Madras says, and while the terminals are grossly restored,
they "may not have rewired exactly as they were originally."
Vokow and her colleagues are now trying to address that question by
examining meth's effects on the serotonin system. Because most meth
users smoke, they're also investigating whether nicotine may play a
neuroprotective role in users.