mGluR5 upregulation and the effects of repeated methamphetamine administration and withdrawal on the rewarding efficacy of ketamine and social interaction.
Yi-Han Liao, Ya-Hui Wang, Li-Han Sun, Wen-Ting Deng, Hsueh-Te Lee, Lung Yu
Toxicology and Applied Pharmacology December 1, 2018 DOI: 10.1016/j.taap.2018.09.035 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Methamphetamine Ketamine MPEP |
| Dose | Methamphetamine 2 mg/kg/day; ketamine 1 mg/kg |
| Duration | 10-day methamphetamine injections followed by 10-day withdrawal |
| Measures | conditioned place preference (CPP), sociability and social novelty test, dopamine-releasing probability, mGluR5 protein expression, EAAT3 expression, Homer2 expression |
| Topics | Ketamine Esketamine |
| Keywords | Dopamine Methamphetamine Superfusion Mglur5 |
| Key points | Repeated methamphetamine administration followed by withdrawal enhanced the rewarding effects of low-dose ketamine and impaired social interaction in mice. These effects were accompanied by reduced dopamine-releasing probability in the nucleus accumbens and increased mGluR5 expression in the hippocampus, and were prevented by the mGluR5 antagonist MPEP, suggesting a role for mGluR5 in these changes. |
Abstract
Repeated, recreational ketamine (KE) or methamphetamine (MA) administration seldom produce neurotoxicity, while combining MA and KE administration have been thought to render changes in neural plasticity and motivational behavior. In this study, we sought to assess whether pre-exposure to multiple MA injections and withdrawal may affect low-dose KE-produced rewarding effects, social interaction behavior and its neurochemical underpinnings. A 10-day MA injections (2 mg/kg/day) and 10-day withdrawal regimen was found to cause reliable behavioral sensitization. While KE (1 mg/kg) induced weak conditioned place preference (CPP), pre-exposure to this MA-withdrawal regimen enhanced such KE CPP magnitude. This MA-withdrawal regimen also caused impairments in the social interaction behavior in the sociability, social novelty test. Compared with the mice undergoing the 10-day saline-withdrawal or MA regimen, mice receiving the 10-day MA-withdrawal regimen exhibited lower dopamine-releasing probability in the nucleus accumbens, inferring the MA-withdrawal regimen-primed preference for KE rewarding effects. Likewise, mice receiving the MA-withdrawal regimen had high expression in mGluR5 protein but unaltered EAAT3, Homer2 expression in hippocampal tissues. Pretreatment with MPEP, an mGluR5 antagonist, prevented the MA-withdrawal regimen-induced increment in the KE CPP magnitude and impairments in social interaction behavior. We, thus, conclude that repeated MA administration and abstinence may enhance KE rewarding effects and produce eminent deficits in social recognition and interest. And these effects correlate with the mGluR5 over-expression and modulation of the KE-stimulating effect on dopamine release.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
- The abuse liability of ketamine: A scoping review of preclinical and clinical studies. Journal of Psychiatric Research May 1, 2022
- Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity. European Journal of Pharmacology June 5, 2024
Cites 2
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- From "Candy Kids" to "Chemi-Kids": a typology of young adults who attend raves in the midwestern United States. Substance Use & Misuse 2005