The Journal of Neuroscience, 2 April 2014, 34(14): 5038-5043; doi: 10.1523/JNEUROSCI.4977-13.2014

Penn Medicine – 1 Avril 2014

Commonly Used Neurological Medication Proves Successful at Blocking Brain’s Reward System Triggers

PHILADELPHIA — Relapse is the most painful and expensive feature of drug addiction—even after addicted individuals have been drug-free for months or years, the likelihood of sliding back into the habit remains high. The National Institute on Drug Abuse estimates that 40 to 60 percent of addicted individuals will relapse, and in some studies the rates are as high as 80 percent at six months after treatment. Though some relapse triggers can be consciously avoided, such as people, places and things related to drug use, other subconscious triggers related to the brain’s reward system may be impossible to avoid— they can gain entry to the unconscious brain, setting the stage for relapse.

Researchers at Penn Medicine’s Center for Studies of Addiction have now found that the drug baclofen, commonly used to prevent spasms in patients with spinal cord injuries and neurological disorders, can help block the impact of the brain’s response to “unconscious” drug triggers well before conscious craving occurs. They suggest that this mechanism has the potential to prevent cocaine relapse. The new findings are reported in the Journal of Neuroscience.

“The study was inspired by patients who had experienced moments of ‘volcanic craving’, being suddenly overcome by the extreme desire for cocaine, but without a trigger that they could put their finger on,” says senior author Anna Rose Childress, PhD, research professor of Psychiatry, director of the Brain-Behavioral Vulnerabilities Division in the Perelman School of Medicine at the University of Pennsylvania. Dr. Childress and colleagues previously found that subliminal drug “reminder cues” (the sights, sounds, smells, and memories of the drug) could activate the brain’s reward circuit. “Now, we wanted to understand whether a medication could inhibit these early brain responses,” said Childress.

Penn Medicine Points to New Ways to Prevent Relapse in Cocaine-Addicted Patients

&roles:David C. S. Roberts · Monique M. Andrews – Psychopharmacology (1997) 131:271–277

Abstract We have previously reported that rats display a circadian pattern of cocaine self-administration if access to drug is limited to 10-min discrete trials that are separated by at least 20 min. In the present study, the pattern of cocaine intake (1.5 mg/kg per injection) was studied in two large groups of animals that were maintained on different 12-h light/dark cycles (3 a.m. to 3 p.m. versus 10 a.m. to 10 p.m.). Regardless of the time of light onset, a circadian pattern of cocaine self-administration was observed. Maximum cocaine intake occurred during the final 6 h of the dark period and was followed by a relative abstinence period during the light phase. This highly predictable pattern of drug taking behavior provided an opportunity to explore the effect of baclofen, a GABAB agonist, on the initiation of self-administration behavior. In two separate studies, acute treatment with baclofen (1.25–5.0 mg/kg) was shown to suppress cocaine intake for at least 4 h. Baclofen had no significant effect on responding for food reinforcement.
Previous results have indicated that baclofen appears to reduce specifically the motivation to respond for cocaine.
Together, these data suggest that baclofen should be considered as a possible pharmacotherapeutic agent in cocaine addiction.

Baclofen suppression of cocaine self-administration demonstration using a discrete trial procedure

Une vidéo qui montre l’efficacité du balofène sur la réduction du craving pour la cocaïne.

Voici le commentaire qu’a fait de Renaud de Beaurepaire concernant l’image située à 1 minute 18 de la vidéo.

« Elle provient d’une équipe d’américains menée par Anna Rose Childress, qui est addictologue.
Cette image provient de cerveau de cocaïnomanes sevrés et à qui on montre un indice de prise de cocaïne, par exemple une ligne blanche, ou quelque chose qui rappelle la drogue et qui déclenche chez eux l’envie d’en reprendre. C’est une chose très connue, c’est un modèle utilisé universellement par l’imagerie cérébrale, c’est très intéressant d’ailleurs.
Quand on montre à quelqu’un qui a été sevré en cocaïne un indice qui lui donne envie d’en prendre, on voit s’allumer son cerveau : toutes sortes de structures impliquées dans la dépendance aux drogues et qui s’appellent l’amygdale, l’insula, le striatum, deviennent hyperactives quand la personne a envie, quand elle a du craving.
L’image allumée de gauche est l’image du craving d’un cerveau qui a envie de drogue.
A droite, les patients ont été traités par baclofène : rien ne s’allume. Voilà donc une démonstration par l’imagerie cérébrale de l’efficacité du baclofène. »