levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN) a novel combination treatment for the prevention of cocaine relapse
dc.contributor.author | Sushchyk, Sarah Ashley | |
dc.date.accessioned | 2015-10-15T15:13:14Z | |
dc.date.available | 2015-10-15T15:13:14Z | |
dc.date.issued | 2015 | |
dc.identifier.uri | http://hdl.handle.net/10713/4849 | |
dc.description | University of Maryland, Baltimore. Pharmaceutical Sciences. Ph.D. 2015 | en_US |
dc.description.abstract | To date, FDA is yet to approve a medication for the treatment of cocaine dependence or for the prevention of cocaine relapse. One promising potential treatment is l-THP, primarily a modest dopamine antagonist. However, l-THP possesses unwanted sedative side effects, which could be difficult to overcome clinically. The present study aims to develop an improved cocaine relapse treatment, creating an l-THP based combination medication. Our preliminary experiments determined l-THP when co-administered with LDN, decreased the sedative effect and increased the efficacy of l-THP. As a result, the focus of this dissertation was placed on the development of l-THP & LDN as a combination medication for the prevention of cocaine relapse. Specific aims used to accomplish the objective were: 1) determine the efficacy of l-THP & LDN combination for attenuation of cocaine seeking behavior as well as minimization of sedative effect of l-THP and 2) investigate the mechanism of l-THP & LDN through β-endorphin release and POMC expression. The combination of l-THP & LDN attenuated reinstatement of conditioned place preference as well as drug-seeking behavior in the reinstatement of cocaine self-administration. Additionally, the l-THP sedative effect observed at the 3mg/kg and 5mg/kg l-THP doses was ameliorated through co-administration of 0.1mg/kg LDN. Taken together, results of the behavioral studies indicate 3mg/kg l-THP & 0.1mg/kg LDN has the greatest potential as a cocaine relapse prevention treatment. This dosage was used to examine the effect of l-THP & LDN on endogenous β-endorphin release and POMC expression. In animals treated with 3mg/kg l-THP & 0.1mg/kg LDN, we correlated the reduction of drug seeking with an increase of plasma β-endorphin and hypothalamic POMC mRNA expression. This to our knowledge is the first study investigating the underlying mechanism of LDN. The research presented in this dissertation establishes l-THP & LDN as novel treatment for the prevention of cocaine relapse and dependence with great potential for future clinical translation. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | levo-tetrahydropalmatine | en_US |
dc.subject | low dose naltrexone | en_US |
dc.subject | relapse prevention | en_US |
dc.subject.lcsh | Drug addiction--Relapse--Prevention | en_US |
dc.subject.mesh | Cocaine | en_US |
dc.subject.mesh | Naltrexone--therapeutic use | en_US |
dc.title | levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN) a novel combination treatment for the prevention of cocaine relapse | en_US |
dc.title.alternative | levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN): A novel combination treatment for the prevention of cocaine relapse | |
dc.type | dissertation | en_US |
dc.contributor.advisor | Wang, Jia Bei | |
dc.identifier.ispublished | No | |
dc.contributor.orcid | 0000-0001-5523-5876 | |
refterms.dateFOA | 2019-02-19T18:03:41Z |