Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.
Yong-Qing Zhang, Hyun Kyu Min, Eunchong Hong, Eunhye Yu, Sun Mi Gu, Seong Shoon Yoon, Dohyun Lee, Jaejun Lee, Jin Tae Hong, Jaesuk Yun
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie November 8, 2023 DOI: 10.1016/j.biopha.2023.115860 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractIn mice, 18 abused drugs (including cocaine, methamphetamine, and several synthetic cannabinoids and cathinones) were tested using intracranial self-stimulation (ICSS) of the medial forebrain bundle to assess their reward-seeking potential. Dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells also correlated with the ICSS threshold. The findings suggest that drug-induced reward-seeking behavior may be linked to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 3-Fluoroethamphetamine methylphenidate cocaine dextroamphetamine alpha-Pyrrolidinobutyrophenone 4'-Fluoro-4-methylaminorex methamphetamine larocaine phentermine paramethoxymethamphetamine phendimetrazine AKB-48 CB-13 JWH-210 JWH-018 4-EA-NBOMe 4-MMA-NBOMe 4-MeO-PCP |
| Keywords | Medicine Psychology |
| Key finding | Dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens significantly correlated with the intracranial self-stimulation threshold after treatment with 18 abused drugs. |
Abstract
Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca2+ signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.