The Role of Nonmuscle Myosin II in Polydrug Memories and Memory Reconsolidation

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) N.Y.), 2018-09, Vol.25 (9), p.391-398
• Main Authors: Briggs, Sherri B, Hafenbreidel, Madalyn, Young, Erica J, Rumbaugh, Gavin, Miller, Courtney A
• Format: Article
• Language: English
• Subjects: Actin; Amphetamines; Amygdala; Brain Hemisphere Functions; Cocaine; Correlation; Drug Abuse; Drug Rehabilitation; Drug Therapy; Fear; Food; Footshock; Genetics; Memory; Methamphetamine; Molecular Structure; Morphine; Myosin; Nicotine; Place preference conditioning; Recidivism; Reinforcement; Rewards; Role; Salts; Stimulants; Unconditioned stimulus
• ISSN: 1072-0502; 1549-5485; 1549-5485
• DOI: 10.1101/lm.046763.117

Using pharmacologic and genetic approaches targeting actin or the actin-driving molecular motor, nonmuscle myosin II (NMII), we previously discovered an immediate, retrieval-independent, and long-lasting disruption of methamphetamine- (METH-) and amphetamine-associated memories. A single intrabasolateral amygdala complex infusion or systemic administration of the NMII inhibitor Blebbistatin (Blebb) is sufficient to produce this disruption, which is selective, having no retrieval-independent effect on memories for fear, food reward, cocaine, or morphine. However, it was unclear if Blebb treatment would disrupt memories of other stimulants and amphetamine class drugs, such as nicotine (NIC) or mephedrone (MEPH; bath salts). Moreover, many individuals abuse multiple drugs, but it was unknown if Blebb could disrupt polydrug memories, or if the inclusion of another substance would render Blebb no longer able to disrupt METH-associated memories. Therefore, the present study had two primary goals: (1) to determine the ability of Blebb to disrupt NIC- or MEPH-associated memories, and (2) to determine the ability of METH to modify other unconditioned stimulus (US) associations' susceptibility to Blebb. To this end, using the conditional place preference model, mice were conditioned to NIC and MEPH alone or METH in combination with NIC, morphine, or foot shock. We report that, unlike METH, there was no retrieval-independent effect of Blebb on NIC- or MEPH-associated memories. However, similar to cocaine, reconsolidation of the memory for both drugs was disrupted. Further, when combined with METH administration, NIC- and morphine-, but not fear-, associated memories were rendered susceptible to disruption by Blebb. Given the high rate of polydrug use and the resurgence of METH use, these results have important implications for the treatment of substance use disorder.