OPEN Foundation

Day: 30 December 2016

Ketamine accelerates fear extinction via mTORC1 signaling

December 30, 2016 / Anxiety disorders / PTSD, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal. Rats received ketamine or saline 24 h after fear conditioning and were then subjected to extinction-training on each of the following three days. Ketamine administration enhanced extinction on the second day of training (i.e., reduced freezing behavior to cue) and produced a long-lasting reduction in freezing on exposure to cue plus context 8 days later. Additionally, ketamine and extinction exposure increased levels of mTORC1 in the medial prefrontal cortex (mPFC), a region involved in the acquisition and retrieval of extinction, and infusion of the selective mTORC1 inhibitor rapamycin into the mPFC blocked the effects of ketamine on extinction. Ketamine plus extinction also increased cFos in the mPFC and administration of a glutamate-AMPA receptor antagonist blocked the effects of ketamine. These results support the hypothesis that ketamine produces long-lasting mTORC1/protein synthesis and activity dependent effects on neuronal circuits that enhance the expression of extinction and could represent a novel approach for the treatment of PTSD.

Girgenti, M. J., Ghosal, S., LoPresto, D., Taylor, J. R., & Duman, R. S. (2017). Ketamine accelerates fear extinction via mTORC1 signaling. Neurobiology of Disease, 100, 1-8. 10.1016/j.nbd.2016.12.026
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Can 3,4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?

December 30, 2016 / Addiction, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By /

Abstract

Treating people with alcohol use disorder has been an important target area for psychedelic research – both in the first studies of the 1950s and during the Psychedelic Renaissance of the last 10 years. To date, most studies have looked at the classical psychedelic drugs as adjuncts to psychotherapy; with attention paid to the psychospiritual aspect of the experience as a central therapeutic process in effecting abstinence from drinking. Psychotherapy assisted with 3,4,-methylenedioxymethamphetamine (MDMA) has never been explored for treating alcohol use disorder. However, MDMA has some unique pharmacological characteristics – particularly its capacity for reducing the fear response and facilitating engagement in therapy around past psychological trauma – that could make it a useful candidate for tackling the core features of alcohol use disorder. This paper briefly describes the burden of alcohol use disorders and the history of psychedelic-assisted psychotherapy in the field of addictions. It gives the theoretical and experimental justification for MDMA-assisted psychotherapy for treating people with alcohol use disorder and introduces a forthcoming study from Bristol and London, UK, exploring the role for MDMA in treating a person with this challenging condition.

Sessa, B. (2016). Can 3, 4,-methylenedioxymethamphetamine therapy be used to treat alcohol use disorder?. Journal of Psychedelic Studies, (0), 1-9. 10.1556/2054.01.2016.003
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30 April - Q&A with Rick Strassman

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