Skip to main content
Springer Nature Link
Log in

The effect of intermittent alcohol vapor or pulsatile heroin on somatic and negative affective indices during spontaneous withdrawal in Wistar rats

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

Abstract

Rationale

Once dependent on alcohol or opioids, negative affect may accompany withdrawal. Dependent individuals are hypothesized to “self-medicate” in order to cope with withdrawal, which promotes escalated alcohol and drug use.

Objectives

The current study aimed to develop a reliable animal model to assess symptoms that occur during spontaneous alcohol and opioid withdrawal.

Methods

Dependence was induced using intermittent alcohol exposure or pulsatile heroin delivery and assessed for the presence of withdrawal symptoms during acute withdrawal by measuring somatic signs, behavior in the forced swim test (FST), and air-puff-induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to 8 weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant alcohol self-administration, and 22-kHz USV production, as well as performance in the elevated plus maze (EPM).

Results

During spontaneous withdrawal from pulsatile heroin or intermittent alcohol vapor, animals displayed increased somatic withdrawal signs, FST immobility, and 22-kHz USV production but did not show any behavioral change in the EPM unless the duration of alcohol exposure was extended to 4 weeks. Following 8 weeks of alcohol vapor exposure, animals displayed somatic withdrawal signs, escalated alcohol self-administration, and increased 22-kHz USVs.

Conclusions

These paradigms provide consistent methods to evaluate the behavioral ramifications, and neurobiological substrates, of alcohol and opioid dependence during spontaneous withdrawal. As immobility in the FST and percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling immobility in the FST, assessment of air-puff-induced 22-kHz USVs could provide an ethologically valid alternative to the FST.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ahmed SH, Walker JR, Koob GF (2000) Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22:413–421

    Article  PubMed  CAS  Google Scholar 

  • Azar MR, Ahmed SH, Lintz R, Gutierrez T, Stinus L, Koob GF (2004) A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal. J Neurosci Methods 135:129–135

    Article  PubMed  CAS  Google Scholar 

  • Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC (2004) Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev 111:33–51

    Article  PubMed  Google Scholar 

  • Barr GA, Zmitrovich A, Hamowy AS, Liu PY, Wang S, Hutchings DE (1998) Neonatal withdrawal following pre- and postnatal exposure to methadone in the rat. Pharmacol Biochem Behav 60:97–104

    Article  PubMed  CAS  Google Scholar 

  • Bell RL, Rodd ZA, Lumeng L, Murphy JM, McBride WJ (2006) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270–288

    Article  PubMed  Google Scholar 

  • Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland CL (2011) Societal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain Med 12:657–667

    Article  PubMed  Google Scholar 

  • Blasig J, Herz A, Reinhold K, Zieglgansberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33:19–38

    Article  PubMed  CAS  Google Scholar 

  • Breese GR, Overstreet DH, Knapp DJ, Navarro M (2005) Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior: inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1a-receptor agonist. Neuropsychopharmacology 30:1662–1669

    Article  PubMed  CAS  Google Scholar 

  • Brown SA, Schuckit MA (1988) Changes in depression among abstinent alcoholics. J Stud Alcohol 49:412–417

    PubMed  CAS  Google Scholar 

  • Burgdorf J, Knutson B, Panksepp J, Shippenberg TS (2001) Evaluation of rat ultrasonic vocalizations as predictors of the conditioned aversive effects of drugs. Psychopharmacology (Berl) 155:35–42

    Article  CAS  Google Scholar 

  • Chartoff E, Sawyer A, Rachlin A, Potter D, Pliakas A, Carlezon WA (2012) Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats. Neuropharmacology 62:167–176

    Article  PubMed  CAS  Google Scholar 

  • Chen SA, O'Dell LE, Hoefer ME, Greenwell TN, Zorrilla EP, Koob GF (2006) Unlimited access to heroin self-administration: independent motivational markers of opiate dependence. Neuropsychopharmacology 31:2692–2707

    Article  PubMed  CAS  Google Scholar 

  • Cochin J, Miller JM, Rosow CE, Grell R, Poulsen JL (1979) The influence of the mode of morphine administration on tolerance and dependence. NIDA Res Monogr 27:36–47

    PubMed  CAS  Google Scholar 

  • Contarino A, Papaleo F (2005) The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. Proc Natl Acad Sci USA 102:18649–18654

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23:238–245

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Page ME, Lucki I (2005a) Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology (Berl) 182:335–344

    Article  CAS  Google Scholar 

  • Cryan JF, Valentino RJ, Lucki I (2005b) Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 29:547–569

    Article  PubMed  CAS  Google Scholar 

  • Devaud LL, Matthews DB, Morrow AL (1999) Gender impacts behavioral and neurochemical adaptations in ethanol-dependent rats. Pharmacol Biochem Behav 64:841–849

    Article  PubMed  CAS  Google Scholar 

  • Duman CH (2010) Models of depression. Vitam Horm 82:1–21

    Article  PubMed  Google Scholar 

  • Fernandes M, Kluwe S, Coper H (1977) Quantitative assessment of tolerance to and dependence on morphine in mice. Naunyn Schmiedebergs Arch Pharmacol 297:53–60

    Article  PubMed  CAS  Google Scholar 

  • Gellert VF, Holtzman SG (1978) Development and maintenance of morphine tolerance and dependence in the rat by scheduled access to morphine drinking solutions. J Pharmacol Exp Ther 205:536–546

    PubMed  CAS  Google Scholar 

  • Getachew B, Hauser SR, Taylor RE, Tizabi Y (2008) Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains. Pharmacol Biochem Behav 91:97–103

    Article  PubMed  CAS  Google Scholar 

  • Getachew B, Hauser SR, Taylor RE, Tizabi Y (2010) Alcohol-induced depressive-like behavior is associated with cortical norepinephrine reduction. Pharmacol Biochem Behav 96:395–401

    Article  PubMed  CAS  Google Scholar 

  • Goeldner C, Lutz PE, Darcq E, Halter T, Clesse D, Ouagazzal AM, Kieffer BL (2011) Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine. Biol Psychiatry 69:236–244

    Article  PubMed  CAS  Google Scholar 

  • Grant BF, Harford TC (1995) Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend 39:197–206

    Article  PubMed  CAS  Google Scholar 

  • Greenwell TN, Funk CK, Cottone P, Richardson HN, Chen SA, Rice KC, Zorrilla EP, Koob GF (2009) Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats. Addict Biol 14:130–143

    Article  PubMed  CAS  Google Scholar 

  • Harris GC, Aston-Jones G (2003) Enhanced morphine preference following prolonged abstinence: association with increased Fos expression in the extended amygdala. Neuropsychopharmacology 28:292–299

    Article  PubMed  CAS  Google Scholar 

  • Harwood HJ, Fountain D, Livermore G (1998) Economic costs of alcohol abuse and alcoholism. Recent Dev Alcohol 14:307–330

    Article  PubMed  CAS  Google Scholar 

  • Hasin DS, Grant BF (2002) Major depression in 6050 former drinkers: association with past alcohol dependence. Arch Gen Psychiatry 59:794–800

    Article  PubMed  Google Scholar 

  • Hay JL, Kaboutari J, White JM, Salem A, Irvine R (2010) Model of methadone-induced hyperalgesia in rats and effect of memantine. Eur J Pharmacol 626:229–233

    Article  PubMed  CAS  Google Scholar 

  • Kalinichev M, Holtzman SG (2003) Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: similarities and differences between acute and chronic dependence. J Pharmacol Exp Ther 304:603–609

    Article  PubMed  CAS  Google Scholar 

  • Kaplan CD (1992) In: de Vries MW (ed) Drug craving and drug use in the daily life of heroin addicts. Cambridge University Press, Cambridge, pp 193–218

    Google Scholar 

  • Kliethermes CL (2005) Anxiety-like behaviors following chronic ethanol exposure. Neurosci Biobehav Rev 28:837–850

    Article  PubMed  CAS  Google Scholar 

  • Knapp DJ, Pohorecky LA (1995) An air-puff stimulus method for elicitation of ultrasonic vocalizations in rats. J Neurosci Methods 62:1–5

    Article  PubMed  CAS  Google Scholar 

  • Knapp DJ, Kampov-Polevoy AB, Overstreet DH, Breese GR, Rezvani AH (1997) Ultrasonic vocalization behavior differs between lines of ethanol-preferring and nonpreferring rats. Alcohol Clin Exp Res 21:1232–1240

    Article  PubMed  CAS  Google Scholar 

  • Knapp DJ, Duncan GE, Crews FT, Breese GR (1998) Induction of Fos-like proteins and ultrasonic vocalizations during ethanol withdrawal: further evidence for withdrawal-induced anxiety. Alcohol Clin Exp Res 22:481–493

    PubMed  CAS  Google Scholar 

  • Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977

    Article  PubMed  Google Scholar 

  • Koob GF (2003) Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 27:232–243

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2009) Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory. Pharmacopsychiatry 42(Suppl 1):S32–S41

    Article  PubMed  Google Scholar 

  • Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902

    Article  PubMed  CAS  Google Scholar 

  • Lopez MF, Becker HC (2005) Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice. Psychopharmacology (Berl) 181:688–696

    Article  CAS  Google Scholar 

  • Lynch HJ, Rivest RW, Wurtman RJ (1980) Artificial induction of melatonin rhythms by programmed microinfusion. Neuroendocrinology 31:106–111

    Article  PubMed  CAS  Google Scholar 

  • Markou A, Kosten TR, Koob GF (1998) Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology 18:135–174

    Article  PubMed  CAS  Google Scholar 

  • Marshall I, Weinstock M (1971) Quantitative method for assessing one symptom of the withdrawal syndrome in mice after chronic morphine administration. Nature 234:223–224

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto I, Burke L, Inoue Y, Wilce PA (2001) Two models of ethanol withdrawal kindling. Nihon Arukoru Yakubutsu Igakkai Zasshi 36:53–64

    PubMed  CAS  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2005) 2005 State estimates of substance use & mental health: substance dependence, abuse, and treatment need. SAMHSA, Rockville, MD

  • Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 national survey on drug use and health. In: Office of Applied Studies (ed) DHHS, Rockville, MD

  • Molina VA, Heyser CJ, Spear LP (1994) Chronic variable stress or chronic morphine facilitates immobility in a forced swim test: reversal by naloxone. Psychopharmacology (Berl) 114:433–440

    Article  CAS  Google Scholar 

  • Moy SS, Knapp DJ, Criswell HE, Breese GR (1997) Flumazenil blockade of anxiety following ethanol withdrawal in rats. Psychopharmacology (Berl) 131:354–360

    Article  CAS  Google Scholar 

  • Moy SS, Knapp DJ, Duncan GE, Breese GR (2000) Enhanced ultrasonic vocalization and Fos protein expression following ethanol withdrawal: effects of flumazenil. Psychopharmacology (Berl) 152:208–215

    Article  CAS  Google Scholar 

  • Mutschler NH, Miczek KA (1998) Withdrawal from a self-administered or non-contingent cocaine binge: differences in ultrasonic distress vocalizations in rats. Psychopharmacology (Berl) 136:402–408

    Article  CAS  Google Scholar 

  • National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DC

    Google Scholar 

  • National Research Council (US) Committee on Guidelines (2003) Guidelines for the care and use of mammals in neuroscience and behavioral research. National Academy Press, Washington, DC

    Google Scholar 

  • Nealey KA, Smith AW, Davis SM, Smith DG, Walker BM (2011) kappa-opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 61:35–42

    Article  PubMed  CAS  Google Scholar 

  • Nunes E, Quitkin F, Brady R, Post-Koenig T (1994) Antidepressant treatment in methadone maintenance patients. J Addict Dis 13:13–24

    Article  PubMed  CAS  Google Scholar 

  • Nutt DJ, Stein DJ (2006) Understanding the neurobiology of comorbidity in anxiety disorders. CNS Spectr 11:13–20

    PubMed  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  Google Scholar 

  • Overstreet DH, Knapp DJ, Breese GR (2004) Similar anxiety-like responses in male and female rats exposed to repeated withdrawals from ethanol. Pharmacol Biochem Behav 78:459–464

    Article  PubMed  CAS  Google Scholar 

  • Pandey SC, Zhang D, Mittal N, Nayyar D (1999) Potential role of the gene transcription factor cyclic AMP-responsive element binding protein in ethanol withdrawal-related anxiety. J Pharmacol Exp Ther 288:866–878

    PubMed  CAS  Google Scholar 

  • Paterson NE, Myers C, Markou A (2000) Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats. Psychopharmacology (Berl) 152:440–446

    Article  CAS  Google Scholar 

  • Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167

    Article  PubMed  CAS  Google Scholar 

  • Portfors CV (2007) Types and functions of ultrasonic vocalizations in laboratory rats and mice. J Am Assoc Lab Anim Sci 46:28–34

    PubMed  CAS  Google Scholar 

  • Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J (2009) Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373:2223–2233

    Article  PubMed  Google Scholar 

  • Rogers J, Wiener SG, Bloom FE (1979) Long-term ethanol administration methods for rats: advantages of inhalation over intubation or liquid diets. Behav Neural Biol 27:466–486

    Article  PubMed  CAS  Google Scholar 

  • Samson HH (1986) Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats. Alcohol Clin Exp Res 10:436–442

    Article  PubMed  CAS  Google Scholar 

  • Schuckit MA, Tipp JE, Bergman M, Reich W, Hesselbrock VM, Smith TL (1997) Comparison of induced and independent major depressive disorders in 2,945 alcoholics. Am J Psychiatry 154:948–957

    PubMed  CAS  Google Scholar 

  • Schulteis G, Markou A, Cole M, Koob GF (1995) Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA 92:5880–5884

    Article  PubMed  CAS  Google Scholar 

  • Schulteis G, Yackey M, Risbrough V, Koob GF (1998) Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze. Pharmacol Biochem Behav 60:727–731

    Article  PubMed  CAS  Google Scholar 

  • Smith AW, Nealey KA, Wright JW, Walker BM (2011) Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems. Neurobiol Learn Mem 96:199–206

    Article  PubMed  CAS  Google Scholar 

  • Steffensen SC, Stobbs SH, Colago EE, Lee RS, Koob GF, Gallegos RA, Henriksen SJ (2006) Contingent and non-contingent effects of heroin on mu-opioid receptor-containing ventral tegmental area GABA neurons. Exp Neurol 202:139–151

    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: regulation by corticotropin-releasing factor. Alcohol Clin Exp Res 26:1494–1501

    Article  PubMed  CAS  Google Scholar 

  • Valenstein ES, Cox VC, Kakolewski JW (1967) Polydipsia elicited by the synergistic action of a saccharin and glucose solution. Science 157:552–554

    Article  PubMed  CAS  Google Scholar 

  • Vendruscolo LF, Schlosburg JE, Misra KK, Chen SA, Greenwell TN, Koob GF (2011) Escalation patterns of varying periods of heroin access. Pharmacol Biochem Behav 98:570–574

    Article  PubMed  CAS  Google Scholar 

  • Vivian JA, Miczek KA (1991) Ultrasounds during morphine withdrawal in rats. Psychopharmacology (Berl) 104:187–193

    Article  CAS  Google Scholar 

  • Vivian JA, Miczek KA (1993) Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters. Psychopharmacology (Berl) 112:66–73

    Article  CAS  Google Scholar 

  • Walker BM (2012) Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process. Alcohol (in press)

  • Walker BM, Koob GF (2007) The gamma-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats. Alcohol Clin Exp Res 31:11–18

    Article  PubMed  CAS  Google Scholar 

  • Walker BM, Koob GF (2008) Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence. Neuropsychopharmacology 33:643–652

    Article  PubMed  CAS  Google Scholar 

  • Walker JR, Ahmed SH, Gracy KN, Koob GF (2000) Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats. Brain Res 854:85–92

    Article  PubMed  CAS  Google Scholar 

  • Walker JR, Chen SA, Moffitt H, Inturrisi CE, Koob GF (2003) Chronic opioid exposure produces increased heroin self-administration in rats. Pharmacol Biochem Behav 75:349–354

    Article  PubMed  CAS  Google Scholar 

  • Walker BM, Rasmussen DD, Raskind MA, Koob GF (2008) Alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol 42:91–97

    Article  PubMed  CAS  Google Scholar 

  • Walker BM, Drimmer DA, Walker JL, Liu T, Mathe AA, Ehlers CL (2010) Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains. Alcohol 44:487–493

    Article  PubMed  CAS  Google Scholar 

  • Walker BM, Valdez GR, McLaughlin JP, Bakalkin G (2012) Targeting Dynorphin/Kappa Opioid Receptor Systems to Treat Alcohol Abuse and Dependence. Alcohol (in press)

  • Wright JS, Panksepp J (2011) Toward affective circuit-based preclinical models of depression: sensitizing dorsal PAG arousal leads to sustained suppression of positive affect in rats. Neurosci Biobehav Rev 35:1902–1915

    Article  PubMed  Google Scholar 

  • Zhang Z, Morse AC, Koob GF, Schulteis G (2007) Dose- and time-dependent expression of anxiety-like behavior in the elevated plus-maze during withdrawal from acute and repeated intermittent ethanol intoxication in rats. Alcohol Clin Exp Res 31:1811–1819

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Support for this research was provided, in part, by R01AA020394-01 from the National Institute on Alcohol Abuse and Alcoholism, RGA 11-014 from the Hope for Depression Research Foundation, research grants from the WSU Alcohol and Drug Abuse Research Program awarded to BMW and DJR according to the State of Washington Initiative Measure No. 171, WSU Department of Psychology research grants awarded to ASP and DJR, and WSU Department of Pharmaceutical Science SURF awards to ASP, DJR, and LJN. The authors would like to thank the NIDA Drug Supply Program for their assistance with the study. The authors are particularly appreciative of the assistance provided by Dr. Jaak Panksepp and Paolo Iacobucci with the technicalities related to USV measurement and lively discussions related to affective states. None of the authors have any financial, personal or organizational conflicts of interest to report in relation to this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health or the State of Washington.

Author information

Authors and Affiliations

  1. Laboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, 100 Dairy Road, 644820, Pullman, WA, 99164-4820, USA

    Angela M. Williams, Daniel J. Reis, Alexa S. Powell, Louis J. Neira, Kathryn A. Nealey, Cole E. Ziegler, Nina D. Kloss, Jessica L. Bilimoria, Chelsea E. Smith & Brendan M. Walker

  2. Translational Addiction Research Center, Washington State University, 100 Dairy Road, 644820, Pullman, WA, 99164-4820, USA

    Brendan M. Walker

  3. Graduate Program in Neuroscience, Washington State University, 100 Dairy Road, 644820, Pullman, WA, 99164-4820, USA

    Brendan M. Walker

Authors
  1. Angela M. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J. Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexa S. Powell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Louis J. Neira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathryn A. Nealey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cole E. Ziegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nina D. Kloss
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jessica L. Bilimoria
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chelsea E. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Brendan M. Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brendan M. Walker.

Additional information

Angela M. Williams, Daniel J. Reis, and Alexa S. Powell contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Williams, A.M., Reis, D.J., Powell, A.S. et al. The effect of intermittent alcohol vapor or pulsatile heroin on somatic and negative affective indices during spontaneous withdrawal in Wistar rats. Psychopharmacology 223, 75–88 (2012). https://doi.org/10.1007/s00213-012-2691-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-012-2691-3

Keywords

Search

Navigation