Lattal lab identifies mechanism that may suppress memories associated with PTSD and addiction

A group of researchers in OHSU’s Lattal lab has discovered that targeting a specific dopamine receptor can promote the suppression of invasive memories in models of PTSD and substance abuse, with implications for treating both disorders. The findings of graduate student Antony Abraham, Kim Neve, Ph.D., and Matthew Lattal, Ph.D., appear in a paper entitled “Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors,” published in the February 10 edition of Neuropsychopharmacology.

Researchers in the Lattal lab based their experiments on the premise that PTSD and addiction can both be thought of as memory disorders wherein normal memory mechanisms get “hijacked,” resulting in very strong and intrusive memories. In the case of PTSD, a traumatic memory evokes an anxiety response when reminders are encountered; in the case of addiction, a drug memory triggered by various associations evokes cravings. Part of a treatment program for both disorders is exposure therapy, which involves exposing the patient to cues that evoke these reactions and allowing the emotional response to occur, then dissipate.

In their paper, the research team modeled this treatment in the lab with rodents by exposing them to cues previously associated with danger, or to cues previously associated with pleasure. They found that if they gave mice a drug that activates a specific class of dopamine receptors (D1/D5 receptors), they could promote learning that fearful contexts are now safe and that drug-associated contexts are no longer associated with drugs.

Scientists have long targeted dopamine receptors associated with natural rewards (positive reinforcement), but new studies show these receptors are also activated in aversive situations (fear conditioning). Still, little was known about the role dopamine plays in memory extinction (when the relation between memory and previously associated events are severed). This research shows that the drug is acting on very general memory mechanisms that are not exclusively tied to reward processes, challenging some widely held assumptions about how dopamine works in memory.

Next steps for the team are to determine where in the brain this mechanism is occurring and to map out a molecular pathway through which the drug may be acting to help identify potential pharmacological interventions.