ArticlePsychopharmacology2021
The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization.
Article in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Dexmedetomidine attenuates methamphetamine-induced hyperthermia and hyperlocomotion in male rats and modulates monoamine dynamics in the anterior hypothalamus.Psychopharmacology · 2026Article
- Pharmacokinetics and concentration-behavioral effect relationships differ between brain subcompartments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Comparative analysis of toxicokinetic profiles of methamphetamine and its metabolites at toxic and therapeutic doses in mice.Forensic toxicology · 2026Article
- Evaluating the reinforcing properties of oxycodone and oxymorphone using intravenous drug self-administration in male rats.Neuropharmacology · 2025Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Human CYP2D6 varies across the estrous cycle in brains of transgenic mice altering drug response.Progress in neuro-psychopharmacology & biological psychiatry · 2024Article
- Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.Advances in neurobiology · 2023Article
- Nanowired Delivery of Mesenchymal Stem Cells with Antioxidant Compound H-290/51 Reduces Exacerbation of Methamphetamine Neurotoxicity in Hot Environment.Advances in neurobiology · 2023Article
- CYP2D in the brain impacts oral hydrocodone analgesia in vivo.Neuropharmacology · 2022Article
- Cannabidiol inhibits methamphetamine-induced dopamine release via modulation of the DRD1-MeCP2-BDNF-TrkB signaling pathway.Psychopharmacology · 2022Article
- Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleCytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats.
methodsTo investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release.
resultsCYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization.
conclusionsCYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.