Validation crisis in animal models of drug addiction: Beyond non-disordered drug use toward drug addiction

  • View
    226

  • Download
    5

Embed Size (px)

Transcript

  • Neuroscience and Biobehavioral Reviews 35 (2010) 172184

    Contents lists available at ScienceDirect

    Neuroscience and Biobehavioral Reviews

    journa l homepage: www.e lsev ier .com/ locate /neubiorev

    Review

    Validatdrug us

    Serge H.a Universit Bob Universit Bo

    a r t i c l

    Key-words:ChoiceSelf-controlRationalitySelf-medicatioDecision-makAbstinenceResilienceVoucher-based treatment

    administration in the rat as a paradigm example. Overall, available evidence shows that when a valuablebehavioral option, even abiologically or physiologically inessential one, ismade available during access tococaine self-administration, most rats readily abstain from cocaine use in favor of the alternative rewardregardless of the amount of past cocaine use. Only a small minority of rats continue to self-administerthe drug despite the opportunity of making a different choice. This pattern of results (i.e., abstinence in

    Contents

    1. Labeli1.1.1.2.1.3.1.4.

    2. Decon2.1.2.2.

    3. Havin3.1.3.2.3.3.3.4.

    4. Choic4.1.4.2.

    CorresponTel.: +33 557

    E-mail add

    0149-7634/$ doi:10.1016/j.most rats; cocaine preference in few rats) maps well onto what is currently known about the epidemiol-ogy of human cocaine addiction. It is thus possible that the minority of cocaine-preferring rats would behomologous to the minority of human cocaine users with a diagnosis of addiction while the remainingmajority of abstinent rats would be resilient to cocaine addiction. Choice could represent an objectivemethod of selection of addicted animals for future research on the neurobiological dysfunctions thatare hypothesized to underlie cocaine addiction. Other competing interpretations of the same pattern ofresults are also discussed at the end of this review.

    2010 Elsevier Ltd. All rights reserved.

    ng, dening and modeling cocaine addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Dependence or addiction: words of choice and choice of words . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Rates of cocaine use and addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Cocaine addiction from a rational choice perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Modeling cocaine addiction in experimental animals: doubts and pitfalls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173struction of animal models of cocaine addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174A brief history of experimental research on animal drug self-administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174Cocaine self-administration in animals: compulsion or expectable response to lack of choice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175

    g the choice during access to cocaine self-administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Introducing choice during access to cocaine: a methodological prolegomenon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176Most animals stop cocaine use when given a choice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176Animals abstain from cocaine use no matter how heavy was past drug use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178Only a minority of animals continue to take cocaine despite choice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

    e as a sieve for cocaine addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179Disease- versus choice-based conceptions of cocaine addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179Resilience and vulnerability to cocaine addiction in animals and humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180

    dence address: Universit Victor-Segalen Bordeaux 2, CNRS, Mouvement Adaptation Cognition, UMR 5227, 146 rue Lo-Saignat, 33076 Bordeaux, France.571 566; fax: +33 556 900 278.ress: sahmed@u-bordeaux2.fr.

    see front matter 2010 Elsevier Ltd. All rights reserved.neubiorev.2010.04.005ion crisis in animal models of drug addiction: Beyond non-disorderede toward drug addiction

    Ahmeda,b,

    rdeaux 2, CNRS, Mouvement Adaptation Cognition, UMR 5227, Francerdeaux 1, CNRS, Mouvement Adaptation Cognition, UMR 5227, France

    e i n f o

    ning

    a b s t r a c t

    In standard drug self-administration settings, animals have no choice than drug use. As a result, seriousdoubt exists about the interpretation of drug use in experimental animals. Is it symptomatic of an under-lying addiction state or merely an expectable response to lack of choice? This incertitude in turn castsa shadow over many behavioral and neurobiological changes that have been well documented in ani-mals following extended drug self-administration. Do they reect pathological dysfunctions or normalneurobiological adaptations? Here I address these questions by focusing on intravenous cocaine self-

  • S.H. Ahmed / Neuroscience and Biobehavioral Reviews 35 (2010) 172184 173

    4.3. Cocaine abstinence in animals and behavioral treatment for cocaine addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1814.4. Current indeterminacy in the interpretation of cocaine abstinence in animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1814.5. Future preclinical research on choice and drug addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182Refer . . . . .

    The goaexperimentanimals. Thadministratanimal specbelow) buto other druspecies. Ovdrug self-adselect drugmerely bybased approis strongly athat dependother types

    1. Labeling

    1.1. Dependwords

    In curreof the AmeManual [DSferred to the(see Sectioncalled for afollowed inHolden, 201of the termmistakewconsequencMaddux anreplacemenAccording tlonger justisuggests a btion is lessother formsfavor of thetoday no rition) and agiven to thein the end othat addictiwith compe

    1.2. Rates o

    CocaineEuropean U2009). Abouleast once incocaine in tof cocaine upast 10 yeaeventually qoccupations

    eir dron. Ievel

    s of ud totrapoonee in tboth

    ents

    cain

    mosperst theRedise at teria 4ewarter che dike cIn coors isultss; mte abcos

    e. Evtionneurrobiation

    odelifalls

    anon-rs invitofrl reg(Voer, bbrainstuds remo usegnosr sciecal bl expasivences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

    l of this review is to provide a novel perspective onal modeling of human drug addiction in laboratorye review mainly focuses on intravenous cocaine self-ion in the rat which is by far the most frequently usedies in experimental addiction research (see Section 2.1t itsmain conclusions should also hopefully be relevantgs of abuse, routes of self-administration and animal

    erall I propose that offering a choice during access toministration could uniquely allow one to identify and

    -addicted rats among those that self-administer drugsdefault of other options. Though the use of a choice-ach in future experimental research on drug addictiondvocated here, it must nevertheless be acknowledgeding on the research question, there is ample room forof self-administration approaches.

    , dening and modeling cocaine addiction

    ence or addiction: words of choice and choice of

    nt ofcial diagnostic nomenclatures (e.g., 4th versionrican Psychiatric Association Diagnostic and StatisticalM] of Mental Disorders), the term dependence is pre-word addiction to label the samebehavioral disorder1.3 below). However, several authors have recently

    reversal of preferencea call that will be apparentlythe forthcoming 5th version of the DSM (Miller and0). As put bluntly by OBrien et al. (2006), the choice