[acb-hsp] Manipulating Memory to Treat Addiction

[peter altschul]

Pavlovian Conditioning for Heroin Addicts: How Manipulating 
Memory Can Treat Addiction
  Mo Costandi, The Guardian April 16, 2012
  A study published today in the journal Science describes a 
simple behavioural procedure that reduces heroin addicts' 
cravings and could also prevent them from relapsing after they've 
kicked the habit.  As I explain in this news story for Nature, 
the procedure involves manipulating addicts' memories of past 
drug use, and could lead to non-pharmacological therapy for 
addiction, as well as psychiatric conditions such as 
post-traumatic stress disorder and phobia.
  Preventing cravings is one of the biggest challenges in the 
treatment of addiction, because they often cause ex-addicts to 
relapse into drug use.  Current treatments effectively relieve 
cravings in the clinic, but not when addicts return to their 
usual environment, because exposure to paraphernalia and other 
stimuli associated with the effects of the drug trigger the 
addict's habitual response of using the drug once again.
  These responses occur because of classical conditioning, a form 
of associative learning discovered by the Russian physiologist 
Ivan Pavlov about a hundred years ago.  Pavlov had built a 
canula-like device for measuring the amount of saliva produced by 
dogs in response to food.  During his experiments, he noticed 
that his dogs began to salivate when the lab assistants who fed 
them entered the room, even if they weren't carrying any food.
  Pavlov speculated that the dogs had learned to associate the 
lab assistants with being fed, and set out to test this idea.  He 
gave the dogs food and rang a bell at the same time.  After 
repeating this several times, the dogs learned to associate the 
bell with the food, so that afterwards they would salivate when 
they heard it.  In the same way, addicts quickly associate 
paraphernalia and other drug-associated cues with the pleasurable 
effects of the drug, so that seeing these cues triggers cravings 
and drug-seeking behaviour.
  Pavlov also noticed, however, that his dogs stopped salivating 
in response to the bell if they heard it several times without 
then receiving food, because this caused them to un-learn the 
association between the two.  This process -- called 'extinction' 
-- forms the basis of cue exposure therapy, in which addicts are 
repeatedly exposed to drug-associated cues and prevented from 
responding to them in the usual way of using the drug.  The idea 
is that this will weaken the learned associations between the 
cues and the effects of the drug.
  Cue exposure therapy relieves cravings in the clinical setting, 
but is less effective in doing so when addicts are re-exposed to 
drugs and associated cues later on.  The new procedure could make 
this therapy more effective.  It combines cue exposure with 
manipulation of a process called memory reconsolidation, in which 
information is retrieved from long-term storage and then 
reactivated so that it can be strengthened.
  Shortly after retrieval the information is rendered temporarily 
unstable and prone to alteration.  The new study builds on 
earlier research by Joe LeDoux and Liz Phelps of New York 
University, showing that reconsolidation can be manipulated 
during this early time window.  In 2009, LeDoux and his 
colleagues published a study which demonstrated that interfering 
with reconsolidation can weaken fear memories in rats:
  The following year, he collaborated with Phelps on a follow-up 
study showed the same procedure can also weaken fear memories in 
humans.  "We used a very simple classical conditioning paradigm 
in which a blue square was paired with a mild electric shock to 
the wrist," Phelps explained.  This caused the participants to 
associate the square with the shocks, and to respond with fear 
when shown the square on its own.
  Afterwards, all the participants underwent extinction sessions, 
in which they were shown the square without receiving shocks.  
One group was briefly shown the square 10 minutes earlier, to 
trigger reconsolidation of the fear memory and coincide it with 
the training.  The others saw the square 6 hours before the 
training.
  "We did the extinction training during reconsolidation, and 
what seems to have happened is that we somehow updated the old 
fear memory," says Phelps.  "In those particular subjects we 
didn't see any evidence of the fear memory returning.  We brought 
the subjects back a year later and showed that the fear did not 
come back in the group that got extinction during 
reconsolidation."
  The new procedure is a variation on this, but also manipulates 
reconsolidation of addicts' memories of past drug use to weaken 
their habitual responses to paraphernalia and other drug-related 
stimuli.  The researchers, from National Institute of Drug 
Dependence at Peking University, show that it effectively reduces 
the cravings induced by such cues for up to six months.
  One series of experiments showed that the procedure effectively 
reduces drug-seeking behaviour in rats.  The rest were performed 
on heroin addicts who were hospitalized throughout the study for 
detoxification, so it remains to be seem whether the procedure 
will be effective in preventing cravings outside of the clinical 
setting.
  "These new findings are powerful confirmation of our earlier 
work using this procedure to diminish the return of fear in rats 
and humans," says LeDoux.  "Hopefully they'll rekindle interest 
in the clinical implications of this paradigm, which can 
potentially improve the efficacy of extinction-based exposure 
therapy for many psychiatric conditions."
  Mo Costandi is a molecular and developmental neurobiologist 
turned science writer.
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