Skip to main content
Log in

Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Existing data strongly suggest that alcohol affects dopamine (DA) neurotransmission in the brain. However, many questions remain about the effects of alcohol on the delicate equilibrium between such neurochemical processes as DA release and uptake. Dysregulation of these processes in the mesolimbic and nigrostriatal systems after chronic alcohol ingestion could be a neuroadaptation contributing to dependence.

Objectives

In the present study, we have employed an alcohol vapor inhalation model to characterize the effects of chronic alcohol exposure on DA dynamics in rat nucleus accumbens (NAc) and caudate putamen (CP) using fast-scan cyclic voltammetry (FSCV) in brain slices. This method provides a unique view of real-time, spatially resolved changes in DA concentration.

Results

We found that chronic alcohol exposure enhanced DA uptake rates in rat NAc and CP. These changes would have the effect of down-regulating extracellular DA levels, presumably a compensatory effect related to increased DA release by repeated alcohol exposure. The sensitivity of terminal release-regulating DA autoreceptors was not different in alcohol-exposed rats compared with alcohol-naïve animals.

Conclusions

The DA uptake changes after chronic alcohol exposure documented here using FSCV may be associated with a compensatory response of the DA system aimed at decreasing DA signaling. Alterations in autoreceptor function may require relatively long lasting alcohol exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Becker HC, Hale RL (1993) Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal “kindling”. Alcohol Clin Exp Res 17:94–98

    Article  PubMed  CAS  Google Scholar 

  • Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    Article  PubMed  CAS  Google Scholar 

  • Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A (2003) Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226–231

    Article  PubMed  CAS  Google Scholar 

  • Brodie MS (2002) Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res 26:1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Budygin EA, Phillips PE, Robinson DL, Kennedy AP, Gainetdinov RR, Wightman RM (2001a) Effect of acute ethanol on striatal dopamine neurotransmission in ambulatory rats. J Pharmacol Exp Ther 297:27–34

    PubMed  CAS  Google Scholar 

  • Budygin EA, Phillips PE, Wightman RM, Jones SR (2001b) Terminal effects of ethanol on dopamine dynamics in rat nucleus accumbens: an in vitro voltammetric study. Synapse 42:77–79

    Article  PubMed  CAS  Google Scholar 

  • Budygin EA, John CE, Mateo Y, Daunais JB, Friedman DP, Grant KA, Jones SR (2003) Chronic ethanol exposure alters presynaptic dopamine function in the striatum of monkeys: a preliminary study. Synapse 50:266–268

    Article  PubMed  CAS  Google Scholar 

  • Budygin EA, Mathews TA, Lapa GB, Jones SR (2005) Local effects of acute ethanol on dopamine neurotransmission in the ventral striatum in C57BL/6 mice. Eur J Pharmacol 523:40–45

    Article  PubMed  CAS  Google Scholar 

  • Cragg SJ (2003) Variable dopamine release probability and short-term plasticity between functional domains of the primate striatum. J Neurosci 23:4378–4385

    PubMed  CAS  Google Scholar 

  • Czachowski CL, Samson HH, Denning CE (1999) Blood ethanol concentrations in rats drinking sucrose/ethanol solutions. Alcohol Clin Exp Res 23:1331–1335

    PubMed  CAS  Google Scholar 

  • Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci USA 90:7966–7969

    Article  PubMed  CAS  Google Scholar 

  • Diana M, Brodie M, Muntoni A, Puddu MC, Pillolla G, Steffensen S, Spiga S, Little HJ (2003) Enduring effects of chronic ethanol in the CNS: basis for alcoholism. Alcohol Clin Exp Res 27:354–361

    Article  PubMed  Google Scholar 

  • Dickinson SD, Sabeti J, Larson GA, Giardina K, Rubinstein M, Kelly MA, Grandy DK, Low MJ, Gerhardt GA, Zahniser NR (1999) Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but no changes in dopamine release in dorsal striatum. J Neurochem 72:148–156

    Article  PubMed  CAS  Google Scholar 

  • Djouma E, Lawrence AJ (2002) The effect of chronic ethanol consumption and withdrawal on mu-opioid and dopamine D(1) and D(2) receptor density in Fawn-Hooded rat brain. J Pharmacol Exp Ther 302:551–559

    Article  PubMed  CAS  Google Scholar 

  • Gonzales RA, Job MO, Doyon WM (2004) The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement. Pharmacol Ther 103:121–146

    Article  PubMed  CAS  Google Scholar 

  • Grace AA (2000) The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction 95(Suppl 2):S119–S128

    Article  PubMed  Google Scholar 

  • Grant KA (1995) The role of 5-HT3 receptors in drug dependence. Drug Alcohol Depend 38:155–171

    Article  PubMed  CAS  Google Scholar 

  • Imperato A, Di Chiara G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–228

    PubMed  CAS  Google Scholar 

  • Jiao X, Pare WP, Tejani-Butt SM (2006) Alcohol consumption alters dopamine transporter sites in Wistar–Kyoto rat brain. Brain Res 1073–1074:175–182

    Article  PubMed  CAS  Google Scholar 

  • Johnson MA, Rajan V, Miller CE, Wightman RM (2006) Dopamine release is severely compromised in the R6/2 mouse model of Huntington’s disease. J Neurochem 97:737–746

    Article  PubMed  CAS  Google Scholar 

  • Jones SR, Garris PA, Wightman RM (1995) Different effects of cocaine and nomifensine on dopamine uptake in the caudate–putamen and nucleus accumbens. J Pharmacol Exp Ther 274:396–403

    PubMed  CAS  Google Scholar 

  • Jones SR, O’Dell SJ, Marshall JF, Wightman RM (1996) Functional and anatomical evidence for different dopamine dynamics in the core and shell of the nucleus accumbens in slices of rat brain. Synapse 23:224–231

    Article  PubMed  CAS  Google Scholar 

  • Jones SR, Mathews TA, Budygin EA (2006) Effect of moderate ethanol dose on dopamine uptake in rat nucleus accumbens in vivo. Synapse 60:251–255

    Article  PubMed  CAS  Google Scholar 

  • Joseph JD, Wang YM, Miles PR, Budygin EA, Picetti R, Gainetdinov RR, Caron MG, Wightman RM (2002) Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D(3) receptors. Neuroscience 112:39–49

    Article  PubMed  CAS  Google Scholar 

  • Laine TP, Ahonen A, Rasanen P, Tiihonen J (2001) Dopamine transporter density and novelty seeking among alcoholics. J Addict Dis 20:91–96

    Article  PubMed  CAS  Google Scholar 

  • Mathews TA, John CE, Lapa GB, Budygin EA, Jones SR (2006) No role of the dopamine transporter in acute ethanol effects on striatal dopamine dynamics. Synapse 60:288–294

    Article  PubMed  CAS  Google Scholar 

  • Mayfield RD, Zahniser NR (2001) Dopamine D2 receptor regulation of the dopamine transporter expressed in Xenopus laevis oocytes is voltage-independent. Mol Pharmacol 59:113–121

    PubMed  CAS  Google Scholar 

  • McGinnis JM, Foege WH (1999) Mortality and morbidity attributable to use of addictive substances in the United States. Proc Assoc Am Physicians 111:109–118

    Article  PubMed  CAS  Google Scholar 

  • Mereu G, Fadda F, Gessa GL (1984) Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain Res 292:63–69

    Article  PubMed  CAS  Google Scholar 

  • Near JA, Bigelow JC, Wightman RM (1988) Comparison of uptake of dopamine in rat striatal chopped tissue and synaptosomes. J Pharmacol Exp Ther 245:921–927

    PubMed  CAS  Google Scholar 

  • Noble EP (1996) Alcoholism and the dopaminergic system: a review. Addict Biol 1:333–348

    Article  PubMed  CAS  Google Scholar 

  • O’Dell LE, Roberts AJ, Smith RT, Koob GF (2004) Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure. Alcohol Clin Exp Res 28:1676–1682

    Article  PubMed  CAS  Google Scholar 

  • Pellegrino SM, Druse MJ (1992) The effects of chronic ethanol consumption on the mesolimbic and nigrostriatal dopamine systems. Alcohol Clin Exp Res 16:275–280

    Article  PubMed  CAS  Google Scholar 

  • Phillips PE, Johns JM, Lubin DA, Budygin EA, Gainetdinov RR, Lieberman JA, Wightman RM (2003) Presynaptic dopaminergic function is largely unaltered in mesolimbic and mesostriatal terminals of adult rats that were prenatally exposed to cocaine. Brain Res 961:63–72

    Article  PubMed  CAS  Google Scholar 

  • Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004) Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci 24:10159–10166

    Article  PubMed  CAS  Google Scholar 

  • Roberto M, Bajo M, Crawford E, Madamba SG, Siggins GR (2006) Chronic ethanol exposure and protracted abstinence alter NMDA receptors in central amygdala. Neuropsychopharmacology 31:988–996

    Article  PubMed  CAS  Google Scholar 

  • Robinson DL, Volz TJ, Schenk JO, Wightman RM (2005) Acute ethanol decreases dopamine transporter velocity in rat striatum: in vivo and in vitro electrochemical measurements. Alcohol Clin Exp Res 29:746–755

    Article  PubMed  CAS  Google Scholar 

  • Rothblat DS, Rubin E, Schneider JS (2001) Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat. Neurosci Lett 300:63–66

    Article  PubMed  CAS  Google Scholar 

  • Samaha AN, Mallet N, Ferguson SM, Gonon F, Robinson TE (2004) The rate of cocaine administration alters gene regulation and behavioral plasticity: implications for addiction. J Neurosci 24:6362–6370

    Article  PubMed  CAS  Google Scholar 

  • Sanna PP, Simpson C, Lutjens R, Koob G (2002) ERK regulation in chronic ethanol exposure and withdrawal. Brain Res 948:186–191

    Article  PubMed  CAS  Google Scholar 

  • Siggins GR, Roberto M, Nie Z (2005) The tipsy terminal: presynaptic effects of ethanol. Pharmacol Ther 107:80–98

    Article  PubMed  CAS  Google Scholar 

  • Tajuddin NF, Druse MJ (1996) Effects of chronic alcohol consumption and aging on dopamine D2 receptors in Fischer 344 rats. Alcohol Clin Exp Res 20:144–151

    Article  PubMed  CAS  Google Scholar 

  • Tang A, George MA, Randall JA, Gonzales RA (2003) Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice. Alcohol Clin Exp Res 27:1083–1089

    Article  PubMed  CAS  Google Scholar 

  • Valdez GR, Roberts AJ, Chan K, Davis H, Brennan M, Zorrilla EP, Koob GF (2002) Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: regulated by corticotropin-releasing factor. Alcohol Clin Exp Res 26:1494–1501

    PubMed  CAS  Google Scholar 

  • Vivian JA, Green HL, Young JE, Majerksy LS, Thomas BW, Shively CA, Tobin JR, Nader MA, Grant KA (2001) Induction and maintenance of ethanol self-administration in cynomolgus monkeys (Macaca fascicularis): long-term characterization of sex and individual differences. Alcohol Clin Exp Res 25:1087–1097

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, Pappas N, Shea C, Piscani K (1996) Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 20:1594–1598

    PubMed  CAS  Google Scholar 

  • Weiner JL, Valenzuela CF (2006) Ethanol modulation of GABAergic transmission: the view from the slice. Pharmacol Ther 111:533–554

    Article  PubMed  CAS  Google Scholar 

  • Weiss F, Porrino LJ (2002) Behavioral neurobiology of alcohol addiction: recent advances and challenges. J Neurosci 22:3332–3337

    PubMed  CAS  Google Scholar 

  • Woodward JJ (2000) Ethanol and NMDA receptor signaling. Crit Rev Neurobiol 14:69–89

    PubMed  CAS  Google Scholar 

  • Wu Q, Reith ME, Kuhar MJ, Carroll FI, Garris PA (2001) Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission. J Neurosci 21:6338–6347

    PubMed  CAS  Google Scholar 

  • Wu Q, Reith ME, Walker QD, Kuhn CM, Carroll FI, Garris PA (2002) Concurrent autoreceptor-mediated control of dopamine release and uptake during neurotransmission: an in vivo voltammetric study. J Neurosci 22:6272–6281

    PubMed  CAS  Google Scholar 

  • Yavich L, Tiihonen J (2000) Ethanol modulates evoked dopamine release in mouse nucleus accumbens: dependence on social stress and dose. Eur J Pharmacol 401:365–373

    Article  PubMed  CAS  Google Scholar 

  • Yim HJ, Gonzales RA (2000) Ethanol-induced increases in dopamine extracellular concentration in rat nucleus accumbens are accounted for by increased release and not uptake inhibition. Alcohol 22:107–115

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Joanne Konstantopoulos for her contributions to the experiments and preparation of the manuscript. This work was supported by Wake Forest University School of Medicine Venture Funds, Alcoholic Beverage Medical Research Foundation (EAB) and National Institutes of Health Grants AA014686 (EAB), AA015830 (TAM), AA014091 and AA013900 (SRJ), AA014445 and AA015179 (BAM).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evgeny A. Budygin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Budygin, E.A., Oleson, E.B., Mathews, T.A. et al. Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen. Psychopharmacology 193, 495–501 (2007). https://doi.org/10.1007/s00213-007-0812-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-0812-1

Keywords

Navigation