From The Quarterly, Winter 2013

NARSAD Grant recipient Dr. Steven R. Laviolette and members of his lab at the University of Western Ontario in Canada have accomplished an impressive feat. This past December they reported online in the journal Neuropharmacology that they had succeeded in blocking the kinds of memories known to activate symptoms of severe anxiety disorders such as post-traumatic stress disorder (PTSD), as well as substance abuse disorders such as morphine addiction.



Memories that doctors and scientists call ‘associative’—terrifying memories of a traumatic episode or pleasurable memories of the ‘high’ obtained from psychoactive drugs—are understood to be activated and conveyed by the transmission of dopamine among nerve cells in the brain. Specifically, cells in the medial prefrontal cortex.



Dr. Laviolette and colleagues wanted to learn more about this process. Specifically, they wanted to pinpoint which of a variety of subtypes of dopamine receptors—molecular ‘keyholes’ on the surface of nerve cells into which dopamine molecules fit like ‘keys’—are relevant in this process. They focused on the so- called ‘D1’ dopamine receptor type.



By experimentally activating this receptor in the rat brain in behaviorally conditioned animals, the scientists found that both negative (‘aversive’) as well as rewarding associative memories could be temporarily blocked. Importantly, they were also able to restore specific memories (using prior addiction to morphine, and memory of its ‘high,’ as an example). This implied that blocking the memory did not destroy underlying memory traces.



“These findings are very important in disorders like PTSD or drug addiction,” Dr. Laviolette comments. “One of the common problems associated with these disorders is the obtrusive recall of memories of fearful experiences in PTSD patients, and for people suffering from addiction, exposure to environmental cues that remind them of the rewarding effects of the drug. This can lead those in treatment to relapse.”



Dr. Laviolette’s team found that the same mechanism in the brain controls recall of both aversive and pleasurable memories. This mechanism not only involves the D1 dopamine receptor, but also, a kind of cellular signaling that depends on a molecule called cyclic AMP (c-AMP). Indeed, memories that were temporarily blocked were restored by administering an inhibitor of c-AMP signaling.



This research is directly relevant to the search for medications that will be able to provide relief for PTSD sufferers, for example, who might be experiencing a flashback. Such medications might also be used to help recovering addicts overcome sudden cravings for getting high. For this reason, Dr. Laviolette considers it important that the temporary memory blockages his team was able to induce didn’t damage the delicate structures of the brain that actually ‘hold’ the stuff of memory.



Steven Laviolette, Ph.D.

2005 and 2007 NARSAD Young Investigator Grantee

Associate Professor

Department of Anatomy and Cell Biology

University of Western Ontario