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Differential influence of morphine sensitization on accumbens shell and core dopamine responses to morphine- and food-conditioned stimuli

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Abstract

Rationale

Sensitization of the incentive and dopamine (DA) stimulant properties of drug-conditioned stimuli (CSs) by repeated exposure to drugs of abuse has been assigned an important role in the genesis of drug addiction.

Objective

To test in rats if morphine-induced sensitization potentiates incentive and DA-releasing properties in the nucleus accumbens (NAc) shell and core elicited by presentation of a morphine-conditioned stimulus(CS) and if this property generalizes to a non-drug-(palatable food, Fonzies)-CS.

Methods

Controls and rats previously sensitized by morphine were trained via three daily sessions consisting of a 10-min presentation of CS (Fonzies filled box, FB) followed by s.c. saline and morphine (1 mg/kg) or by standard food and Fonzies. Rats were implanted with microdialysis probes and the next-day incentive reactions and NAc shell and core DA were monitored during CS presentation and subsequent morphine (1 mg/kg) administration or Fonzies feeding.

Results

Morphine sensitization increased incentive and NAc shell and core DA responses to morphine-CS. Morphine conditioning per se increased incentive reactions and NAc shell but not core DA responses to FB presentation. Morphine sensitization potentiated incentive responses but did not affect NAc shell and core DA responses to Fonzies-CS. Fonzies conditioning increased incentive reactions and NAc core but not shell DA responses to FB presentation.

Conclusions

These observations confirm the prediction of the incentive sensitization theory in the case of drug-CS but not of non-drug-CS. NAc DA might be differentially involved in the expression of incentive sensitization of drug- and non-drug-CSs, thus providing a clue for the abnormal incentive properties of drug CSs.

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References

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (4th edn), Washington, D.C.

  • Aragona BJ, Cleaveland NA, Stuber GD, Day JJ, Carelli RM, Wightman RM (2008) Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. J Neurosci 28(35):8821–8831

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1997) Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17(2):851–861

    PubMed  CAS  Google Scholar 

  • Bassareo V, De Luca MA, Aresu M, Aste A, Ariu T, Di Chiara G (2003) Differential adaptive properties of accumbens shell dopamine response to ethanol as a drug and as a motivational stimulus. Eur J Neurosci 17(7):1465–1472

    Article  PubMed  Google Scholar 

  • Bassareo V, De Luca MA, Di Chiara G (2007) Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex. Psychopharmacol 191:689–703

    Article  CAS  Google Scholar 

  • Bassareo V, Musio P, Di Chiara G (2011) Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli. Psychopharmacol 214:687–697

    Article  CAS  Google Scholar 

  • Ben-Shahar O, Ahmed SH, Koob GF, Ettenberg A (2004) The transition from controlled to compulsive drug use is associated with a loss of sensitization. Brain Res 995(1):46–54

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Di Chiara G (1999) Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate–putamen in rats sensitized to morphine. Neuroscience 90(2):447–455

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Di Chiara G (2000) Differential changes in accumbens shell and core dopamine in behavioral sensitization to nicotine. Eur J Pharmacol 387(3):R23–R25

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Solinas M, Di Chiara G (2000) Psychostimulant sensitization: differential changes in accumbal shell and core dopamine. Eur J Pharmacol 388(1):69–76

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Valentini V, Di Chiara G (2008) Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission. J Neurochem 106(4):1586–1593

    Article  PubMed  CAS  Google Scholar 

  • Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305(5686):1014–1017

    Article  PubMed  CAS  Google Scholar 

  • Di Chiara G (1995) The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38:95–137

    Article  PubMed  Google Scholar 

  • Di Chiara G (1998) A motivational learning hypothesis of the role of dopamine in compulsive drug use. J Psychopharmacol 12:54–67

    Article  PubMed  Google Scholar 

  • Di Chiara G (1999) Drug addiction as dopamine-dependent associative learning disorder. Eur J Pharmacol 375:13–30

    Article  PubMed  Google Scholar 

  • Di Chiara G, Tanda G, Frau R, Carboni E (1993) On the preferential release of dopamine in the nucleus accumbens by amphetamine: further evidence obtained by vertically implanted concentric dialysis probes. Psychopharmacol 112:98–402

    Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8(11):1481–1489

    Article  PubMed  CAS  Google Scholar 

  • Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward. The role of amygdale–ventral striatal subsystems. Ann New York Acad Sci 877:412–438

    Article  CAS  Google Scholar 

  • Fiorino DF, Phillips AG (1999a) Facilitation of sexual behavior in male rats following d-amphetamine-induced behavioral sensitization. Psychopharmacology 42(2):200–208

    Article  Google Scholar 

  • Fiorino DF, Phillips AG (1999b) Facilitation of sexual behavior and enhanced dopamine efflux in the nucleus accumbens of male rats after d-amphetamine-induced behavioral sensitization. J Neurosci 19:456–463

    PubMed  CAS  Google Scholar 

  • Harmer CJ, Phillips GD (1998) Enhanced appetitive conditioning following repeated pretreatment with D-amphetamine. Behav Pharmacol 9:299–308

    Google Scholar 

  • Harmer CJ, Phillips GD (1999) Enhanced dopamine efflux in the amygdala by a predictive, but not a non-predictive, stimulus: facilitation by prior repeated damphetamine. Neuroscience 90(1): 119–130

    Article  PubMed  CAS  Google Scholar 

  • ICD-10 Classification of Mental and Behavioural Disorders (1993) World Health Organization

  • Kalivas PW, Duffy P (1987) Sensitization to repeated morphine injection in the rat: possible involvement of A10 dopamine neurons. J Pharmacol Exp Ther 241:204–212

    PubMed  CAS  Google Scholar 

  • Kalivas PW, Duffy P (1990) Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse 5(1):48–58

    Article  PubMed  CAS  Google Scholar 

  • Klein ED, Gehrke BJ, Green TA, Zentall TR, Bardo MT (2007) Repeated cocaine experience facilitates sucrose-reinforced operant responding in enriched and isolated rats. Learn Motiv 16(2):190–209

    Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacol 24:97–129

    Article  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Gronli J, Spiga S, Di Chiara G (2006a) Preferential increase of extracellular dopamine in the rat nucleus accumbens shell as compared to that in the core during acquisition and maintenance of intravenous nicotine selfadministration. Psychopharmacology 184(3–4):435–446

    Article  PubMed  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Di Chiara G (2006b) Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55, 212–2 self-administration. Psychopharmacology 188(1):63–74

    Article  PubMed  CAS  Google Scholar 

  • Lecca D, Valentini V, Cacciapaglia F, Acquas E, Di Chiara G (2007a) Reciprocal effects of response contingent and noncontingent intravenous heroin on in vivo nucleus accumbens shell versus core dopamine in the rat: a repeated sampling microdialysis study. Psychopharmacol 194(1):103–116

    Article  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Acquas E, Di Chiara G (2007b) Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat. Psychopharmacology 191:653–667

    Article  PubMed  CAS  Google Scholar 

  • Martinez D, Narendran R, Foltin RW, Slifstein M, Hwang DR, Broft A, Huang Y, Cooper TB, Fischman MW, Kleber HD, Laruelle M (2007) Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry 164(4):622–629

    Article  PubMed  Google Scholar 

  • Martinez D, Carpenter KM, Liu F, Slifstein M, Broft A, Friedman AC, Kumar D, Van Heertum R, Kleber HD, Nunes E (2011) Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment. Am J Psychiatry 168(6):634–641

    Article  PubMed  Google Scholar 

  • Martinez D, Saccone PA, Liu F, Slifstein M, Orlowska D, Grassetti A, Cook S, Broft A, Van Heertum R, Comer SD (2012) Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction. Biol Psychiatry 71(3):192–198

    Article  PubMed  CAS  Google Scholar 

  • Mendez IA, Williams MT, Bhavsara A, Lu AP, Bizon JL, Setlow B (2009) Long-lasting sensitization of reward-directed behavior by amphetamine. Behav Brain Res 201:74–79

    Article  PubMed  CAS  Google Scholar 

  • Narendran R, Martinez D (2008) Cocaine abuse and sensitization of striatal dopamine transmission: a critical review of the preclinical and clinical imaging literature. Synapse 62(11):851–869

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (2003) Guidelines for the care and use of mammals in Neuroscience and behavioral research. The National Academies Press, Washington, D.C.

  • Nocjar C, Panksepp J (2002) Chronic intermittent amphetamine pretreatment enhances future appetitive behavior for drug- and natural-reward: interaction with environmental variables. Behav Brain Res 128(2):189–203

    Article  PubMed  CAS  Google Scholar 

  • O’Brien CP, Childress AR, McLellan AT, Ehrman R (1992) Classical conditioning in drug-dependent humans, In: The neurobiology of drug and alcohol addiction. Ann New York Acad Sci 654:400–15

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, New York

    Google Scholar 

  • Pontieri FE, Tanda G, Di Chiara G (1995) Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc Natl Acad Sci USA 92:12304–12308

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257

    Article  PubMed  CAS  Google Scholar 

  • Ranaldi R, Egan J, Kest K, Fein M, Delamater AR (2009) Repeated heroin in rats produces locomotor sensitization and enhances appetitive Pavlovian and instrumental learning involving food reward. Pharmacol Biochem Behav 91(3):351–357

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev 28:309–369

    Article  PubMed  Google Scholar 

  • Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 91:251–268

    Article  PubMed  CAS  Google Scholar 

  • Tanda G, Bassareo V, Di Chiara G (1996) Mianserin markedly and selectively increases extracellular dopamine in the prefrontal cortex as compared to the nucleus accumbens of the rat. Psychopharmacology 123:127–130

    Article  PubMed  CAS  Google Scholar 

  • Tanda G, Pontieri FE, Di Chiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276:2048–2050

    Article  PubMed  CAS  Google Scholar 

  • Taylor JR, Jentsch JD (2001) Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine (“Ecstasy”). Biol Psychiatr 50(2):137–143

    Article  CAS  Google Scholar 

  • Vezina P (2004) Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27(8):827–839

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Chang L, Wang GJ, Fowler JS, Ding YS, Sedler M, Logan J, Franceschi D, Gatley J, Hitzemann R, Gifford A, Wong C, Pappas N (2001) Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry 158(12):2015–2021

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Bozarth MA (1987) A psychomotor theory of addiction. Psychol Rev 94:469–492

    Article  PubMed  CAS  Google Scholar 

  • Wyvell CL, Berridge KC (2000) Intra-accumbens amphetamine increases the conditioned incentive salience of sucrose reward: enhancement of reward “wanting” without enhanced “liking” or response feinforcement. J Neurosci 20(21):8122–8130

    PubMed  CAS  Google Scholar 

  • Wyvell CL, Berridge KC (2001) Incentive sensitization by previous amphetamine exposure: increased cue-triggered “wanting” for sucrose reward. J Neurosci 21(19):7831–7840

    PubMed  CAS  Google Scholar 

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Acknowledgments

Flavia Cucca gratefully acknowledges Sardinia Regional Government for the financial support of her PhD scholarship (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013 — Axis IV Human Resources, Objective l.3, Line of Activity l.3.1.).

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Correspondence to Gaetano Di Chiara.

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Bassareo, V., Cucca, F., Cadoni, C. et al. Differential influence of morphine sensitization on accumbens shell and core dopamine responses to morphine- and food-conditioned stimuli. Psychopharmacology 225, 697–706 (2013). https://doi.org/10.1007/s00213-012-2856-0

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  • DOI: https://doi.org/10.1007/s00213-012-2856-0

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