Author:
Choi Sanghoon,Du Yijuan,Wokosin David L.,Graves Steven M.
Abstract
AbstractMethamphetamine (meth) is an addictive psychostimulant and illicit use presents significant personal and socioeconomic harm. Behavioral studies support the involvement of the dorsal striatum in drug-seeking but stimulant induced dysfunction in this region is understudied. The dorsal striatum can be subdivided into the dorsomedial (DMS) and dorsolateral (DLS) striatum with the DMS implicated in goal-directed and DLS in habitual behaviors; both regions are primarily composed of GABAergic direct (dSPNs) and indirect pathway (iSPNs) spiny projection neurons. To examine the effect of repeated meth on SPNs, mice were administered meth (2 mg/kg) for ten consecutive days and intrinsic excitability, dendritic excitability, and spine density were examined. DMS iSPN intrinsic excitability was increased at 1 day but decreased at 21 days of abstinence. In contrast, DMS dSPN intrinsic excitability was unchanged at either timepoint. Dendritic excitability and spine densities were unaltered in DMS iSPNs and dSPNs at 1 and 21 days of abstinence. The effect of repeated meth on iSPN excitability was specific to the DMS; DLS iSPN intrinsic excitability, dendritic excitability, and spine density were unchanged at 1 and 21 days of abstinence. These findings point toward DMS iSPN dysfunction in meth use disorders with differential dysfunction dependent on abstinence duration.
Funder
National Institute on Drug Abuse
Publisher
Springer Science and Business Media LLC
Reference78 articles.
1. Winkelman, T. N. A. et al. Evaluation of amphetamine-related hospitalizations and associated clinical outcomes and costs in the United States. JAMA Netw. Open 1, e183758. https://doi.org/10.1001/jamanetworkopen.2018.3758 (2018).
2. NSDUH. Center for Behavioral Health Statistics and Quality. 2017 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration, Rockville, MD (2018).
3. Shearer, R. D., Howell, B. A., Bart, G. & Winkelman, T. N. A. Substance use patterns and health profiles among US adults who use opioids, methamphetamine, or both, 2015–2018. Drug Alcohol Depend. 214, 108162. https://doi.org/10.1016/j.drugalcdep.2020.108162 (2020).
4. Han, B. et al. Methamphetamine overdose deaths in the US by sex and race and ethnicity. JAMA Psychiat. 78, 564–567. https://doi.org/10.1001/jamapsychiatry.2020.4321 (2021).
5. Freyberg, Z. et al. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat. Commun. 7, 10652. https://doi.org/10.1038/ncomms10652 (2016).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献