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Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration

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Abstract

Rationale

WIN 55,212-2, a potent cannabinoid receptor 1 agonist, is self-administered by animals to evaluate abuse liability of cannabinoids, but to date no information is yet available about its effects on dopaminergic transmission during active response-contingent administration.

Objectives

This study monitored the changes of extracellular dopamine (DA) in the nucleus accumbens (NAc) shell and core during active intravenous WIN 55,212-2 self-administration (SA).

Methods

Rats, implanted with a jugular catheter and bilateral intracerebral chronic cannulae, were trained for 3 weeks to self-administer WIN 55,212-2 (12.5 μg/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, than switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA.

Results

Dialysate DA increased during WIN 55,212-2 SA starting from the 1st week in the NAc shell and on the 2nd week in the core. The increase of dialysate DA in the NAc shell was larger than that in the core on all weeks. Dialysate DA did not change during extinction sessions in spite of active nose poking.

Conclusions

Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding.

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References

  • 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 17:851–861

    PubMed  CAS  Google Scholar 

  • Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW (2002) Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl) 160:353–361

    Article  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 90:447–455

    Article  PubMed  CAS  Google Scholar 

  • Cadoni C, Di Chiara G (2000) Differential changes in accumbens shell and core dopamine in behavioural sensitization to nicotine. Eur J Pharmacol 387: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 388:69–76

    Article  PubMed  CAS  Google Scholar 

  • Caine SB, Koob GF (1993) Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science 260:1814–1816

    Article  PubMed  CAS  Google Scholar 

  • Camp DM, Robinson TE (1992) On the use of multiple probe insertions at the same site for repeated intracerebral microdialysis experiments in nigrostriatale dopamine system of rats. J Neurochem 58:1706–1715

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Kandel DB, Davies M (1997) Relationships between frequency and quantity of marijuana use and last year proxy dependence among adolescents and adults in the United States. Drug Alcohol Depend 46:53–67

    Article  PubMed  CAS  Google Scholar 

  • D’Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC, Cippari SM, Grego JD, Kullnig RK, Daley GT (1992) Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl) indole agonists of the cannabinoid receptor. J Med Chem 35:124–135

    Article  PubMed  CAS  Google Scholar 

  • Datla KP, Ahier RG, Young AM, Gray JA, Joseph MH (2002) Conditioned appetitive stimulus increases extracellular dopamine in the nucleus accumbens of the rat. Eur J Neurosci 16:1987–1993

    Article  PubMed  CAS  Google Scholar 

  • Di Chiara G (2002) From rats to humans and return: testing addiction hypotheses by combined PET imaging and self-reported measures of psychostimulant effects. Commentary on Volkow et al. ‘Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies’. Behav Pharmacol 13:371–377

    PubMed  Google Scholar 

  • Di Chiara G, Tanda G, Carboni E (1996) Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity. Behav Pharmacol 7:640–657

    Article  PubMed  Google Scholar 

  • Fattore L, Cossu G, Martellotta CM, Fratta W (2001) Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-n rats. Psychopharmacology 156:410–416

    Article  PubMed  CAS  Google Scholar 

  • Fumero B, Guadalupe T, Valladares F, Mora F, O’Neill RD, Mas M, Gonzalez-Mora JL (1994) Fixed versus removable microdialysis probes for in vivo neurochemical analysis: implications for behavioral studies. J Neurochem 63:1407–1415

    Article  PubMed  CAS  Google Scholar 

  • Georgieva J, Luthman J, Mohringe B, Magnusson O (1993) Tissue and microdialysate changes after repeated and permanent probe implantation in the striatum of freely moving rats. Brain Res Bull 31:463–470

    Article  PubMed  CAS  Google Scholar 

  • Gobert A, Millan MJ (1999) Modulation of dialysate levels of dopamine, noradrenaline, and serotonin (5-HT) in the frontal cortex of freely-moving rats by (−)-pindolol alone and in association with 5-HT reuptake inhibitors: comparative roles of beta-adrenergic, 5-HT1A, and 5-HT1B receptors. Neuropsychopharmacology 21:268–284

    Article  PubMed  CAS  Google Scholar 

  • Hemby SE, Co C, Koves TR, Smith JE, Dworkin SI (1997) Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology (Berl) 133:7–16

    Article  CAS  Google Scholar 

  • Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20:7489–7495

    PubMed  CAS  Google Scholar 

  • Jacobs EH, Smit AB, de Vries TJ, Schoffelmeer AN (2005) Long-term gene expression in the nucleus accumbens following heroin administration is subregion-specific and depends on the nature of drug administration. Addict Biol 10:91–100

    Article  PubMed  CAS  Google Scholar 

  • Justinova Z, Tanda G, Redhi GH, Goldberg SR (2003) Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology (Berl) 169:135–140

    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 self-administration. Psychopharmacology 184:435–446

    Article  PubMed  CAS  Google Scholar 

  • Lecca D, Valentini V, Cacciapaglia F, Acquas E, Di Chiara G (2006b) Differential neurochemical and behavioral adaptation to cocaine after response contingent and non-contingent exposure in the rat. Psychopharmacology (in press)

  • Martin-Fardon R, Sandillon F, Thibault J, Privat A, Vignon J (1997) Long-term monitoring of extracellular dopamine concentration in the rat striatum by a repeated microdialysis procedure. J Neurosci Methods 72:123–135

    Article  PubMed  CAS  Google Scholar 

  • Moore H, Stuckman S, Sarter M, Bruno JP (1995) Stimulation of cortical acetylcholine efflux by FG 7142 measured with repeated microdialysis sampling. Synapse 21:324–331

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic, Sidney

    Google Scholar 

  • Pettit HO, Justice JB Jr (1991) Effect of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens. Brain Res 539:94–102

    Article  PubMed  CAS  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 

  • Pop E (1999) Cannabinoids, endogenous ligands and synthetic analogs. Curr Opin Chem Biol 3:418–425

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Camp DM (1991) The feasibility of repeated microdialysis for within-subjects design experiments: studies on mesostriatal dopamine system. In: Robins TE, Justice JB (eds). Microdialysis in the Neurosciences. Elsevier, Amsterdam, pp 189–234

    Google Scholar 

  • Tanda G, Goldberg SR (2003) Cannabinoids: reward, dependence, and underlying neurochemical mechanisms—a review of recent preclinical data. Psychopharmacology (Berl) 169:115–134

    Article  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 

  • Tanda G, Munzar P, Goldberg SR (2000) Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci 11:1073–1074

    Google Scholar 

  • Van Etten ML, Anthony JC (1999) Comparative epidemiology of initial drug opportunities and transitions to first use: marijuana, cocaine, hallucinogens and heroin. Drug Alcohol Depend 54:117–125

    Article  PubMed  Google Scholar 

  • Ventura R, Cabib S, Alcaro A, Orsini C, Puglisi-Allegra S (2003) Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release. J Neurosci 23:1879–1885

    PubMed  CAS  Google Scholar 

  • Westerink BH, Kawahara Y, De Boer P, Geels C, De Vries JB, Wikstrom HV, Van Kalkeren A, Van Vliet B, Kruse CG, Long SK (2001) Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum. Eur J Pharmacol 412:127–138

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 120:10–20

    Article  CAS  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the advice of Dr. Elio Acquas with the TH immunohistochemistry and of Dr. Luigi Minerba with the statistical analysis; the supply of the SA cages by Dr. Steve Goldberg and Dr. Gianluigi Tanda is also acknowledged. This study was supported by funds from Ministero dell’Università e della Ricerca, progetti di Ricerca Nazionale Bando 2003, from the Centre of Excellence for Studies On Dependence.

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Authors and Affiliations

  1. Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Daniele Lecca, Fabio Cacciapaglia, Valentina Valentini & Gaetano Di Chiara

  2. Centre of Excellence for Studies on the Neurobiology of Addiction, Cagliari, Italy

    Daniele Lecca, Valentina Valentini & Gaetano Di Chiara

  3. Institute of Neuroscience, Consiglio Nazionale delle Ricerche (CNR), Section of Cagliari, Cagliari, Italy

    Gaetano Di Chiara

Authors
  1. Daniele Lecca
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  2. Fabio Cacciapaglia
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  3. Valentina Valentini
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  4. Gaetano Di Chiara
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Correspondence to Gaetano Di Chiara.

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Lecca, D., Cacciapaglia, F., Valentini, V. et al. 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, 63–74 (2006). https://doi.org/10.1007/s00213-006-0475-3

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  • DOI: https://doi.org/10.1007/s00213-006-0475-3

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