Research on Cocaine - Archives - National Institute on Drug Abuse

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Methylphenidate for Comorbid Cocaine Abuse, ADHD In an inpatient study with 14 non-treatment-seeking volunteers, Columbia University researcher Dr. Stephanie Collins and colleagues reported that a regimen of 40-60 mg/day of sustained-release methylphenidate (SR-MPH) reduced ratings on scales of “feel high,” “good drug effect,” and other measures of cocaine’s reinforcing effects among seven abusers affected by attention deficit hyperactivity disorder (ADHD). The medication increased the cardiovascular effects seen with cocaine alone, but not to dangerous levels. Although preliminary, the findings suggest that a therapeutic approach of using slow-acting 43 <strong>Research</strong> Findings Volume 21, Number 1 (October 2006) stimulants to reduce craving for cocaine—parallel to the use of methadone or buprenorphine in opiate addiction—may be possible for cocaine-addicted patients with ADHD. Although the researchers did not formally assess SR-MPH’s effects on participants’ ADHD symptoms, they did not note any obvious benefits. Source • Drug and Alcohol Dependence 82(2):158-167, 2006.
44 <strong>Research</strong> Findings Brain Mechanism Turns Off Cocaine-Related Memory in Rats An exploration of memory’s molecular basis suggests potential novel therapeutic approaches to cue-induced craving. By Patrick Zickler, NIDA Notes Contributing Writer Scientists at the University of California, Irvine, have added to evidence that a brain enzyme controls key memory processes that link drug experiences, the surroundings in which they take place, and the urge to repeat them. In a series of experiments, inhibiting the enzyme attenuated a rat behavior that is a laboratory stand-in for human cueinduced drug-seeking. The findings suggest that in the future, therapeutically manipulating levels of the enzyme might cut addicted individuals’ vulnerability to environmental triggers for drug craving and abuse. The NIDA-funded scientists, Drs. Courtney Miller and John Marshall, focused on the enzyme in an attempt to elucidate the ways cellular activities promote cue-induced drug-seeking. “Although studies have established that nerve cells in the core of the nucleus accumbens are critically involved,” Dr. Miller says, “we haven’t had much information about the molecular mechanisms that transform environmental cues into an urge to repeat drugassociated behavior.” One likely candidate for a role in the process, however, was extracellular signal-regulated kinase (ERK). This enzyme is known both to foster the new cellular connections that register emotional and object recognition memories in the brain and to be affected by cocaine. The researchers explored ERK’s role in a behavior called conditioned place preference (CPP). By exhibiting CPP— lingering in a part of a cage where it has had a drug experience— an animal indicates that it remembers the experience, associates it with the preferred cage area, and is seeking to have it again (for more on CPP, see “Animal Experiments Volume 21, Number 1 (October 2006) in Addiction Science,” NIDA Notes, Vol. 20, No. 5). In previous research, blocking ERK activity in the nucleus accumbens (NAc) prior to exposing rats to drugs prevented them from developing CPP. Drs. Miller and Marshall reasoned that if blocking ERK forestalls initial formation of the memory links underlying CPP, it might also weaken links that had already been formed. The potential therapeutic implications would be significant if this were so; they would suggest that manipulating ERK might be a means to disrupt drug-environment associations that are already established by the time patients begin therapy. To test their hypothesis, the researchers administered cocaine to rats daily for 9 days, after which the rats exhibited CPP whenever they were placed back in their test cage. The researchers then conducted a series of trials and assays that showed: • CPP involves activation of ERK: Rats that lingered in the cocaine-associated area of the test cage had higher ERK levels in the core area of the NAc than a group of rats that had not been exposed to cocaine or a third
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Keeping up with Drug Abuse
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Research on Cocaine - Archives - National Institute on Drug Abuse

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