Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration.

A figure from this study.

Featured Paper of the Month – March 2019.

Abuse of opioids including oxycodone is very prevalent in the US. Researchers in the laboratory of Jean Lud Cadet in the NIDA IRP have shown that when rats are given access to oxycodone for several hours, some of the rats will increase the amount of the drug in a very steep fashion whereas others will only take moderate quantities of the drug. They also found, however, that, after a month of withdrawal from oxycodone, all those rats had decreased levels of mu opioid receptor protein in the dorsal striatum, a brain region that is important for habit forming. Decreases in striatal opioid receptor protein expression in these rats may be one of the reasons why addicted patients relapse to opioid seeking.

Publication Information

Blackwood, Christopher A; Hoerle, Reece; Leary, Michael; Schroeder, Jennifer; Job, Martin O; McCoy, Michael T; Ladenheim, Bruce; Jayanthi, Subramaniam; Cadet, Jean Lud

Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration. Journal Article

In: Mol Neurobiol, 2018, ISSN: 1559-1182 (Electronic); 0893-7648 (Linking).

Abstract | Links

@article{Blackwood:2018aa,

title = {Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration.},

author = {Christopher A Blackwood and Reece Hoerle and Michael Leary and Jennifer Schroeder and Martin O Job and Michael T McCoy and Bruce Ladenheim and Subramaniam Jayanthi and Jean Lud Cadet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30155791},

doi = {10.1007/s12035-018-1318-z},

issn = {1559-1182 (Electronic); 0893-7648 (Linking)},

year  = {2018},

date = {2018-08-28},

urldate = {2018-08-28},

journal = {Mol Neurobiol},

address = {Molecular Neuropsychiatry Research Branch, NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.},

abstract = {Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Here, we sought to identify potential neurobiological consequences of withdrawal from escalated and non-escalated oxycodone self-administration in rats. To reach these goals, we used short-access (ShA) (3 h) and long-access (LgA) (9 h) exposure to oxycodone self-administration followed by protracted forced abstinence. After 31 days of withdrawal, we quantified mRNA and protein levels of opioid receptors in the rat dorsal striatum and hippocampus. Rats in the LgA, but not the ShA, group exhibited escalation of oxycodone SA, with distinction of two behavioral phenotypes of relatively lower (LgA-L) and higher (LgA-H) oxycodone takers. Both LgA, but not ShA, phenotypes showed time-dependent increases in oxycodone seeking during the 31 days of forced abstinence. Rats from both LgA-L and LgA-H groups also exhibited decreased levels of striatal mu opioid receptor protein levels in comparison to saline and ShA rats. In contrast, mu opioid receptor mRNA expression was increased in the dorsal striatum of LgA-H rats. Moreover, hippocampal mu and kappa receptor protein levels were both increased in the LgA-H phenotype. Nevertheless, hippocampal mu receptor mRNA levels were decreased in the two LgA groups whereas kappa receptor mRNA expression was decreased in ShA and LgA oxycodone groups. Decreases in striatal mu opioid receptor protein expression in the LgA rats may serve as substrates for relapse to drug seeking because these changes occur in rats that showed incubation of oxycodone seeking.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}