<?xml version="1.0" encoding="utf-8" ?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.2 20190208//EN"
                  "JATS-archivearticle1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="1.2" article-type="other">
<front>
<journal-meta>
<journal-id></journal-id>
<journal-title-group>
<journal-title>Journal for Reproducibility in
Neuroscience</journal-title>
</journal-title-group>
<issn publication-format="electronic">2670-3815</issn>
<publisher>
<publisher-name>Publishers of Trial and Error</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<title-group>
<article-title>Have we reproduced Rat Park? Conceptual but not direct
replication of the protective effects of social and environmental
enrichment in addiction</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0002-0972-3788</contrib-id>
<name>
<surname>Khoo</surname>
<given-names>Shaun Yon-Seng</given-names>
</name>
<xref ref-type="aff" rid="aff-0"/>
</contrib>
<aff id="aff-0">
<institution-wrap>
<institution>Department of Pharmacology and Physiology, Faculty of
Medicine, Université de Montréal, Montreal, Quebec, Canada</institution>
</institution-wrap>
</aff>
</contrib-group>
<pub-date date-type="pub" publication-format="electronic">
<day>13</day>
<month>08</month>
<year>2020</year>
</pub-date>
<volume>1</volume>
<elocation-id>reproduced-rat-park</elocation-id>
<permissions>
<license license-type="CC-BY-NC" xlink:href="https://creativecommons.org/licenses/by-nc/4.0/">
<license-p>Creative Commons Attribution-NonCommercial 4.0 International
License</license-p>
</license>
</permissions>
<self-uri xlink:href="https://jrn.trialanderror.org/pub/reproduced-rat-park">This pub is available from https://jrn.trialanderror.org/pub/reproduced-rat-park</self-uri>
</article-meta>
</front>
<body>
<sec id="abstract">
  <title><bold>Abstract</bold></title>
  <p>The Rat Park studies are classic experiments in addiction
  neuroscience, yet they have not been successfully replicated directly
  and several serious methodological criticisms have been raised.
  However, the conceptual reproducibility of the Rat Park studies is
  supported by both contemporaneous and subsequent research.
  Contemporaneous research on social and environmental enrichment
  frequently found social isolation rendered rats less sensitive to the
  effects of drugs of abuse. The Rat Park studies therefore confirmed
  the importance of social and environmental enrichment and extended
  this literature to suggest that enrichment reduced opioid consumption.
  Subsequent studies have also demonstrated social and environmental
  enrichment reduces drug consumption. However, there are also several
  papers reporting no effects of enrichment (or ‘negative’ results) and
  caveats from studies that show genes, age, sex and drug of abuse are
  all important parameters. While the Rat Park studies did not use
  methods that are reliable by current standards, enrichment has been
  shown to reliably reduce opioid consumption and this effect can
  generalise to other drugs of abuse.</p>
  <p><bold>Keywords: </bold><italic>Rat Park, Addiction, Environment,
  Social, Enrichment, Housing</italic></p>
  <graphic id="nsl5ae8ux36" mimetype="image" mime-subtype="png" xlink:href="https://assets.pubpub.org/zqt0ujuz/image-61691161317092.png" />
  <p></p>
  <p></p>
  <graphic id="nrbree3j3bo" mimetype="image" mime-subtype="png" xlink:href="https://assets.pubpub.org/pzrlppew/image-71691160815460.png" />
  <p></p>
</sec>
<sec id="reviewers-comments">
  <title>Reviewer’s Comments</title>
  <p>[file element]</p>
  <p></p>
</sec>
<sec id="references">
  <title><bold>References</bold></title>
  <p>Gage SH, Sumnall HR. Rat Park: How a rat paradise changed the
  narrative of addiction. Addiction. 2019;114(5):917-22.</p>
  <p>Alexander BK, Coambs RB, Hadaway PF. The effect of housing and
  gender on morphine self-administration in rats. Psychopharmacology.
  1978;58(2):175-9.</p>
  <p>Coambs RB, Alexander BK, Davis CM, Hadaway PF, Tressel WR. A drug
  dispenser to measure individual drinking in rat colonies. Pharmacology
  Biochemistry and Behavior. 1980;13(4):593-5.</p>
  <p>Alexander BK, Beyerstein BL, Hadaway PF, Coambs RB. Effect of early
  and later colony housing on oral ingestion of morphine in rats.
  Pharmacology Biochemistry and Behavior. 1981;15(4):571-6.</p>
  <p>Hadaway PF, Alexander BK, Coambs RB, Beyerstein B. The effect of
  housing and gender on preference for morphine-sucrose solutions in
  rats. Psychopharmacology. 1979;66(1):87-91.</p>
  <p>Alexander BK, Hadaway PF. Opiate addiction: The case for an
  adaptive orientation. Psychological Bulletin. 1982;92(2):367-81.</p>
  <p>Heirene R. A call for replications of addiction research: Which
  studies should we replicate &amp; what constitutes a “successful”
  replication? PsyArXiV Preprints. 2020.</p>
  <p>Petrie BF. Environment is not the most important variable in
  determining oral morphine consumption in Wistar rats. Psychological
  Reports. 1996;78(2):391-400.</p>
  <p>Simons DJ. The value of direct replication. Perspectives on
  Psychological Science. 2014;9(1):76-80.</p>
  <p>Stroebe W, Strack F. The alleged crisis and the illusion of exact
  replication. Perspectives on Psychological Science.
  2014;9(1):59-71.</p>
  <p>Nosek BA, Errington TM. What is replication? PLOS Biology.
  2020;18(3):e3000691.</p>
  <p>Fuentes VO, Hunt WB, Crossland J. The production of morphine
  tolerance and physical dependence by the oral route in the rat.
  Psychopharmacology. 1978;59(1):65-9.</p>
  <p>Hill SY, Powell BJ. Cocaine and morphine self-administration:
  Effects of differential rearing. Pharmacology Biochemistry and
  Behavior. 1976;5(6):701-4.</p>
  <p>Rushton R, Steinberg H. Reactions to drugs influenced by early
  experience. Animal Behaviour. 1966;14(4):585.</p>
  <p>Welch BL, Welch AS, Adams JG, Garriss KB, Piland J, Eskay R, et al.
  Graded effect of social stimulation upon d-amphetamine toxicity,
  aggressiveness and heart and adrenal weight. Journal of Pharmacology
  and Experimental Therapeutics. 1966;151(3):331-8.</p>
  <p>Katz DM, Steinberg H. Long-term isolation in rats reduces morphine
  response. Nature. 1970;228(5270):469-71.</p>
  <p>Baumel I, DeFeo JJ, Lal H. Decreased potency of CNS depressants
  after prolonged social isolation in mice. Psychopharmacologia.
  1969;15(2):153-8.</p>
  <p>Kazmaier K, Butcher RE, Senter RJ, Stutz RM. Rearing conditions and
  ethanol consumption by rats. Quarterly Journal of Studies on Alcohol.
  1973;34(2):520-4.</p>
  <p>Bardo MT, Rowlett JK, Harris MJ. Conditioned place preference using
  opiate and stimulant drugs: A meta-analysis. Neuroscience &amp;
  Biobehavioral Reviews. 1995;19(1):39-51.</p>
  <p>Schenk S, Hunt T, Colle L, Amit Z. Isolation versus grouped housing
  in rats: differential effects of low doses of heroin in the place
  preference paradigm. Life Sciences. 1983;32(10):1129-34.</p>
  <p>Schenk S, Ellison F, Hunt T, Amit Z. An examination of heroin
  conditioning in preferred and nonpreferred environments and in
  differentially housed mature and immature rats. Pharmacology
  Biochemistry and Behavior. 1985;22(2):215-20.</p>
  <p>El Rawas R, Thiriet N, Lardeux V, Jaber M, Solinas M. Environmental
  enrichment decreases the rewarding but not the activating effects of
  heroin. Psychopharmacology. 2009;203(3):561-70.</p>
  <p>Schenk S, Hunt T, Klukowski G, Amit Z. Isolation housing decreases
  the effectiveness of morphine in the conditioned taste aversion
  paradigm. Psychopharmacology. 1987;92(1):48-51.</p>
  <p>Smith JK, Neill JC, Costall B. The influence of postweaning housing
  conditions on drug-induced conditioned taste aversion. Pharmacology
  Biochemistry and Behavior. 1998;59(2):379-86.</p>
  <p>Schenk S, Hunt T, Malovechko R, Robertson A, Klukowski G, Amit Z.
  Differential effects of isolation housing on the conditioned place
  preference produced by cocaine and amphetamine. Pharmacology
  Biochemistry and Behavior. 1986;24(6):1793-6.</p>
  <p>Lespine L-F, Tirelli E. No evidence that wheel-running exercise
  impacts cocaine conditioned place preference in male C57BL/6J mice.
  Behavioural Brain Research. 2019;365:110-3.</p>
  <p>Zakharova E, Miller J, Unterwald E, Wade D, Izenwasser S. Social
  and physical environment alter cocaine conditioned place preference
  and dopaminergic markers in adolescent male rats. Neuroscience.
  2009;163(3):890-7.</p>
  <p>Chauvet C, Lardeux V, Jaber M, Solinas M. Brain regions associated
  with the reversal of cocaine conditioned place preference by
  environmental enrichment. Neuroscience. 2011;184:88-96.</p>
  <p>Solinas M, Thiriet N, Rawas RE, Lardeux V, Jaber M. Environmental
  enrichment during early stages of life reduces the behavioral,
  neurochemical, and molecular effects of cocaine.
  Neuropsychopharmacology. 2009;34(5):1102-11.</p>
  <p>Freese L, Almeida FB, Heidrich N, Hansen AW, Steffens L, Steinmetz
  A, et al. Environmental enrichment reduces cocaine neurotoxicity
  during cocaine-conditioned place preference in male rats. Pharmacology
  Biochemistry and Behavior. 2018;169:10-5.</p>
  <p>Ribeiro Do Couto B, Aguilar MA, Lluch J, Rodríguez-Arias M, Miñarro
  J. Social experiences affect reinstatement of cocaine-induced place
  preference in mice. Psychopharmacology. 2009;207(3):485-98.</p>
  <p>Solinas M, Chauvet C, Thiriet N, El Rawas R, Jaber M. Reversal of
  cocaine addiction by environmental enrichment. Proceedings of the
  National Academy of Sciences. 2008;105(44):17145-50.</p>
  <p>Wongwitdecha N, Marsden CA. Isolation rearing prevents the
  reinforcing properties of amphetamine in a conditioned place
  preference paradigm. European Journal of Pharmacology.
  1995;279(1):99-103.</p>
  <p>Yates JR, Beckmann JS, Meyer AC, Bardo MT. Concurrent choice for
  social interaction and amphetamine using conditioned place preference
  in rats: Effects of age and housing condition. Drug and Alcohol
  Dependence. 2013;129(3):240-6.</p>
  <p>Thiriet N, Gennequin B, Lardeux V, Chauvet C, Decressac M, Janet T,
  et al. Environmental enrichment does not reduce the rewarding and
  neurotoxic effects of methamphetamine. Neurotox Res.
  2011;19(1):172-82.</p>
  <p>Bozarth MA, Murray A, Wise RA. Influence of housing conditions on
  the acquisition of intravenous heroin and cocaine self-administration
  in rats. Pharmacology Biochemistry and Behavior. 1989;33(4):903-7.</p>
  <p>Hofford RS, Chow JJ, Beckmann JS, Bardo MT. Effects of
  environmental enrichment on self-administration of the short-acting
  opioid remifentanil in male rats. Psychopharmacology.
  2017;234(23):3499-506.</p>
  <p>Imperio CG, McFalls AJ, Hadad N, Blanco-Berdugo L, Masser DR,
  Colechio EM, et al. Exposure to environmental enrichment attenuates
  addiction-like behavior and alters molecular effects of heroin
  self-administration in rats. Neuropharmacology. 2018;139:26-40.</p>
  <p>Boyle AE, Gill K, Smith BR, Amit Z. Differential effects of an
  early housing manipulation on cocaine-induced activity and
  self-administration in laboratory rats. Pharmacology Biochemistry and
  Behavior. 1991;39(2):269-74.</p>
  <p>van der Veen R, Piazza PV, Deroche-Gamonet V. Gene–environment
  interactions in vulnerability to cocaine intravenous
  self-administration: a brief social experience affects intake in
  DBA/2J but not in C57BL/6J mice. Psychopharmacology.
  2007;193(2):179-86.</p>
  <p>Westenbroek C, Perry AN, Becker JB. Pair housing differentially
  affects motivation to self-administer cocaine in male and female rats.
  Behavioural Brain Research. 2013;252:68-71.</p>
  <p>Schenk S, Robinson B, Amit Z. Housing conditions fail to affect the
  intravenous self-administration of amphetamine. Pharmacology
  Biochemistry and Behavior. 1988;31(1):59-62.</p>
  <p>Puhl MD, Blum JS, Acosta-Torres S, Grigson PS. Environmental
  enrichment protects against the acquisition of cocaine
  self-administration in adult male rats, but does not eliminate
  avoidance of a drug-associated saccharin cue. Behavioural
  Pharmacology. 2012;23(1):43-53.</p>
  <p>Gauthier JM, Lin A, Nic Dhonnchadha BÁ, Spealman RD, Man H-Y,
  Kantak KM. Environmental enrichment facilitates cocaine-cue
  extinction, deters reacquisition of cocaine self-administration and
  alters AMPAR GluA1 expression and phosphorylation. Addiction Biology.
  2017;22(1):152-62.</p>
  <p>Thiel KJ, Sanabria F, Pentkowski NS, Neisewander JL. Anti-craving
  effects of environmental enrichment. International Journal of
  Neuropsychopharmacology. 2009;12(9):1151-6.</p>
  <p>Chauvet C, Lardeux V, Goldberg SR, Jaber M, Solinas M.
  Environmental enrichment reduces cocaine seeking and reinstatement
  induced by cues and stress but not by cocaine.
  Neuropsychopharmacology. 2009;34(13):2767-78.</p>
  <p>Cantin L, Lenoir M, Augier E, Vanhille N, Dubreucq S, Serre F, et
  al. Cocaine is low on the value ladder of rats: Possible evidence for
  resilience to addiction. PLoS ONE. 2010;5(7):e11592.</p>
  <p>Huynh C, Fam J, Ahmed SH, Clemens KJ. Rats quit nicotine for a
  sweet reward following an extensive history of nicotine use. Addiction
  Biology. 2015;22(1):142-51.</p>
  <p>Lenoir M, Cantin L, Vanhille N, Serre F, Ahmed SH. Extended heroin
  access increases heroin choices over a potent nondrug alternative.
  Neuropsychopharmacology. 2013;38(7):1209-20.</p>
  <p>Madsen HB, Ahmed SH. Drug versus sweet reward: greater attraction
  to and preference for sweet versus drug cues. Addiction Biology.
  2015;20(3):433-44.</p>
  <p>Ahmed SH, Lenoir M, Guillem K. Neurobiology of addiction versus
  drug use driven by lack of choice. Current Opinion in Neurobiology.
  2013;23(4):581-7.</p>
  <p>Newman EL, Leonard MZ, Arena DT, de Almeida RMM, Miczek KA. Social
  defeat stress and escalation of cocaine and alcohol consumption: Focus
  on CRF. Neurobiology of Stress. 2018;9:151-65.</p>
  <p>Venniro M, Shaham Y. An operant social self-administration and
  choice model in rats. Nature Protocols. 2020.</p>
  <p>Venniro M, Russell TI, Ramsey LA, Richie CT, Lesscher HMB,
  Giovanetti SM, et al. Abstinence-dependent dissociable central
  amygdala microcircuits control drug craving. Proceedings of the
  National Academy of Sciences. 2020:202001615.</p>
  <p>Venniro M, Russell TI, Zhang M, Shaham Y. Operant social reward
  decreases incubation of heroin craving in male and female rats.
  Biological Psychiatry. 2019;86(11):848-56.</p>
  <p>Venniro M, Zhang M, Caprioli D, Hoots JK, Golden SA, Heins C, et
  al. Volitional social interaction prevents drug addiction in rat
  models. Nature Neuroscience. 2018;21(11):1520-9.</p>
</sec>
</body>
<back>
</back>
</article>