Determining patterns of addiction reveals keys to brain response

Dawn Wiseman

For those studying drug abuse and the complicated question of relapse, Jane Stewart (Center for Studies in Behavioral Neuro-biology, CSBN) is a well-known name. Her research into the neurobiology and behavioural aspects of drug use and abuse is seminal in the field.

“I really got into it through an interest in the neurobiology of motivation,” she explained.

Drugs of abuse have their effects in areas of the brain related to motivation. “For example, most drugs which turn off pain also tend to turn on pleasure.” That’s a pretty powerful motivator.

Stewart’s career at Concordia began before it was Concordia. “I was the third person hired into the Department of Psychology at Sir George in 1963,” she said. More than 40 years later, her CV reveals the expected: nearly 200 refereed publications, almost a dozen books or chapters, uncountable conference proceedings, and many, many grad students.

Indeed, her former students now hold key positions at McGill, Université de Montréal and the University of Chicago, to name a few. Several of these relationships have borne fruitful collaborations, perhaps none more than her work with Harriet de Wit, now in the Department of Psychiatry at the University of Chicago.

From 1981 to 1984, still early days for Psychology’s doctoral program, Stewart and de Wit jointly published three papers (the third with Roelof Eikelboom) examining relapse in drug use among laboratory rats.

“Relapse is the toughest problem to address in treatment,” Stewart said. “We know how drug use affects the brain. We know how habits are acquired. But breaking a habit completely is different. Essentially, we are asking people to stop doing something they want to do.”

Her work with de Wit underlined that not taking drugs isn’t sufficient to break the hold they have on the brain and behaviour, and in fact, that relapse can occur even after “extended periods of abstinence.” Later work has shown that relapse in both humans and lab animals can be induced by re-exposure to the drug, by exposure to drug-related cues (people, places and situations the subject associates with drug use) and by exposure to stress.

The original findings have been embraced by those studying drug treatment. In 2003, the journal Psychopharmacology published a special edition commemorating Stewart’s and de Wit’s work. The introduction to the issue showed that citations of the original publications have increased exponentially over time.

Most of Stewart’s funding has come through NSERC and the Canadian Institutes for Health Research (CIHR). “CIHR has been responsible for the larger grants, some of which have originally been for five years, and gone on for 20.” It is the kind of support required to develop a body of work with such impact.

Even after all this recognition, Stewart is not ready to rest on her laurels. “These are very complex problems. People are paying attention to our models for treatment of addiction. We’ve learned a lot about the brain, and a lot about brain changes during drug taking, but we’re not there yet.”

She continues to study relapse from a neurobiological perspective. “I’m looking at what systems of the brain are activated and by what means.” She’s also studying the long-term effects of drugs of abuse on the central nervous system. “Drugs of abuse change the brain in fundamental ways. There are structural and neurochemical changes, many of which are within systems that mediate appetitive behaviour.”

And Stewart is still asking questions that take her research in new directions. “One emerging area is focused on efforts to find ways of improving the extinction of responses to cues associated with drugs.”

She said that there appear to be similarities between the mechanisms that maintain fear and anxiety responses to cues previously associated with aversive or traumatic events and those that maintain responses to cues previously associated with drugs. The emotional responses elicited by these cues are very difficult to extinguish.

She’s also interested in other aspects of the drug/brain connection. “Consider that we have receptors in the brain for just about every type of drug we abuse. We seem to be naturally equipped to respond to such drugs. What’s the evolutionary significance of that?”