ArticlePsychopharmacology2013
Tolerance and sensitization to chronic escalating dose heroin following extended withdrawal in Fischer rats: possible role of mu-opioid receptors.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Using miniscopes and deep learning to compare neurobehavioral representations of psychostimulant and opioid self-administration.Addiction neuroscience · 2025Article
- Drug Self-Administration, Drug-Specific Behaviors, and Neurobehavioral Deep Learning Analyses.Addiction neuroscience · 2025Article
- Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor.MedComm · 2022Review
- Cannabis Addiction and the Brain: a Review.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2018Review
- Adolescent oxycodone self administration alters subsequent oxycodone-induced conditioned place preference and anti-nociceptive effect in C57BL/6J mice in adulthood.Neuropharmacology · 2016Article
- Sugar addiction: the state of the science.European journal of nutrition · 2016Review
- Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence.Translational psychiatry · 2015Article
- Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Behavioral flexibility and response selection are impaired after limited exposure to oxycodone.Learning & memory (Cold Spring Harbor, N.Y.) · 2014Article
- Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6 J mice.Psychopharmacology · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
RATIONALE/
objectivesHeroin addiction is characterized by recurrent cycles of drug use, abstinence, and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity.
methodsMale Fischer rats were exposed chronically to escalating doses of heroin (7.5-75 mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [(3)H]DAMGO and [(35)S]GTPγS assays.
resultsThe depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified.
conclusionsAspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density.
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