ArticlePsychopharmacology2014
Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
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- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.Pharmaceutics · 2021Article
- Effects of Drugs of Abuse on the Blood-Brain Barrier: A Brief Overview.Frontiers in neuroscience · 2020Review
- Placental trophoblast transfer of opioids following exposures to individual or mixtures of opioidsExperimental biology and medicine (Maywood, N.J.) · 2019Article
- Narcotic Addiction in Failed Back Surgery Syndrome.Cell transplantation · 2019Review
- Loperamide cardiotoxicity: "A Brief Review".Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2018Review
- The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse.Fluids and barriers of the CNS · 2017Review
- Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain.Current neuropharmacology · 2017Review
- Pharmacophore-based discovery of inhibitors of a novel drug/proton antiporter in human brain endothelial hCMEC/D3 cell line.British journal of pharmacology · 2015Article
- Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions.Pharmaceutical research · 2015Review
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleTransport across the BBB is a determinant of the rate and extent of drug distribution in the brain. Heroin exerts its effects through its principal metabolites 6-monoacetyl-morphine (6-MAM) and morphine. Morphine is a known substrate of P-glycoprotein (P-gp) at the blood-brain-barrier (BBB) however, little is known about the interaction of heroin and 6-MAM with P-gp.
objectiveThe objective of this paper is to study the role of the P-gp-mediated efflux at the BBB in the behavioral and molecular effects of heroin and morphine.
methodsThe transport rates of heroin and its main metabolites, at the BBB, were measured in mice by in situ brain perfusion. We then examined the effect of inhibition of P-gp on the acute nociception, locomotor activity, and gene expression modulations induced by heroin and morphine. The effect of P-gp inhibition during the acquisition of morphine-induced place preference was also studied.
resultsInhibition of P-gp significantly increased the uptake of morphine but not that of heroin nor 6-MAM. Inhibition of P-gp significantly increased morphine-induced acute analgesia and locomotor activity but did not affect the behavioral effects of heroin; in addition, acute transcriptional responses to morphine were selectively modulated in the nucleus accumbens. Increasing morphine uptake by the brain significantly increased its reinforcing properties in the place preference paradigm.
conclusionsThe present study demonstrated that acute inhibition of P-gp not only modulates morphine-induced behavioral effects but also its transcriptional effects and reinforcing properties. This suggests that, in the case of morphine, transport across the BBB is critical for the development of dependence.
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