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Lorazepam reinstates punishment-suppressed remifentanil self-administration in rats

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Abstract

Rationale

We recently described a reinstatement procedure that models relapse to drug abuse in cases where abstinence results from aversive consequences of drug use. The potential value of this punishment-based model of relapse depends on its sensitivity to relapse-inducing events that are ineffective in the widely used extinction-based model.

Objectives

It is known that certain drugs can have antipunishment effects, but these drugs have not been tested in the punishment-based reinstatement procedure. Therefore, the effects of the benzodiazepine, lorazepam, were examined using punishment-based and extinction-based reinstatement procedures.

Methods

Rats self-administered the opioid, remifentanil (4 μg/kg per infusion). Two punishment groups were trained with response-contingent footshock that suppressed baseline rates of responding to zero. In an extinction group, remifentanil delivery was discontinued, and baseline responding stabilized at a low rate (mean=0.06 responses/min). Lorazepam (0.08–10 mg/kg, IP) was given during test sessions with the shock contingency discontinued for both punishment groups. Remifentanil delivery was maintained during testing in one punishment group but not the other.

Results

Lorazepam reinstated self-administration responding in both punishment groups but not in the extinction group. Priming injections of heroin reinstated responding in both the punishment and extinction groups, but combining heroin and lorazepam did not enhance reinstatement.

Conclusions

This is the first demonstration that a trigger for relapse may have different effects depending on whether aversive conditioning contributed to the achievement of abstinence. It may be important to consider potential antipunishment effects of both abused drugs and therapeutic agents in the treatment of individuals with a history of drug abuse.

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References

  • Azrin NH, Holz WC (1966) Punishment. In: Honig WK (ed) Operant behavior: areas of research and application. Prentice-Hall, Englewood Cliffs, pp 380–447

    Google Scholar 

  • Baldwin HA, Wall TL, Schuckit MA, Koob GF (1991) Differential effects of ethanol on punished responding in the P and NP rats. Alcohol Clin Exp Res 15:700–704

    CAS  PubMed  Google Scholar 

  • Bergman J, Johanson CE (1991) The effects of electric shock on responding maintained by cocaine in rhesus monkeys. Pharmacol Biochem Behav 14:423–426

    Article  Google Scholar 

  • Bergman J, Katz JL (1998) Behavioral pharmacology of cocaine and the determinants of abuse liability. In: Higgins ST, Katz JL (eds) Cocaine abuse: behavior, pharmacology, and clinical applications. Academic, New York, pp 51–79

    Google Scholar 

  • Bialik RJ, Pappas BA, Pusztay W (1982) Chlordiazepoxide-induced released responding in extinction and punishment-conflict procedures is not altered by neonatal forebrain norepinephrine depletion. Pharmacol Biochem Behav 16:279–283

    Article  CAS  PubMed  Google Scholar 

  • Brewer C (1993) Recent developments in disulfiram treatment. Alcohol Alcohol 28:383–395

    CAS  PubMed  Google Scholar 

  • Brown RT, Wagner AR (1964) Resistance to punishment and extinction following training with shock or nonreinforcement. J Exp Psychol 68:503–507

    CAS  PubMed  Google Scholar 

  • Buckland C, Mellanby J, Gray JA (1986) The effects of compounds related to gamma-aminobutyrate and benzodiazepine receptors on behavioural responses to anxiogenic stimuli in the rat: extinction and successive discrimination. Psychopharmacology 88:285–295

    Article  CAS  PubMed  Google Scholar 

  • Burman S (1997) The challenge of sobriety: natural recovery without treatment and self-help groups. J Subst Abuse 9:41–61

    Article  CAS  PubMed  Google Scholar 

  • Carroll ME (1998) Acquisition and reacquisition (relapse) of drug abuse: modulation by alternative reinforcers. NIDA Res Monogr 169:6–25

    CAS  PubMed  Google Scholar 

  • Chait LD, Wenger GR, McMillan DE (1981) Effects of phencyclidine and ketamine on punished and unpunished responding by pigeons. Pharmacol Biochem Behav 15:145–148

    Article  CAS  PubMed  Google Scholar 

  • Childress AR, McLellan AT, O’Brien CP (1985) Behavioral therapies for substance abuse. Int J Addict 20:947–969

    CAS  PubMed  Google Scholar 

  • Commissaris RL, Hill TJ, McMiller LV Jr, Kleinsorge RJ (1995) Initial subsensitivity to anxiolytic treatments on conflict behavior in rats: parametric studies across drug classes. Pharmacol Biochem Behav 51:391–396

    Article  CAS  PubMed  Google Scholar 

  • Cook L, Davidson AB (1973) Effects of behaviorally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven, New York, pp 327–345

    Google Scholar 

  • Criswell HE, Breese GR (1989) A conflict procedure not requiring deprivation: evidence that chronic ethanol treatment induces tolerance to the anticonflict action of ethanol and chlordiazepoxide. Alcohol Clin Exp Res 13:680–685

    CAS  PubMed  Google Scholar 

  • Crowley TJ (1985) Doctors’ drug abuse reduced during contingency-contracting treatment. Alcohol Drug Res 6:299–307

    PubMed  Google Scholar 

  • Cunningham JA, Lin E, Ross HE, Walsh GW (2000) Factors associated with untreated remissions from alcohol abuse or dependence. Addict Behav 25:317–321

    Article  CAS  PubMed  Google Scholar 

  • Feldon J, Gray JA (1981) The partial reinforcement extinction effect after treatment with chlordiazepoxide. Psychopharmacology 73:269–275

    CAS  PubMed  Google Scholar 

  • File SE (1985) Tolerance to the behavioral actions of benzodiazepines. Neurosci Biobehav Rev 9:113–121

    Article  CAS  PubMed  Google Scholar 

  • File SE, Wilks LJ, Mabbutt PS (1988) Withdrawal, tolerance and sensitization after a single dose of lorazepam. Pharmacol Biochem Behav 31:937–940

    Article  CAS  PubMed  Google Scholar 

  • Fontana DJ, Commissaris RL (1992) Anxiolytic-like effects of alpha-2-adrenoceptor agonists on conflict behavior in the rat: pre- versus postsynaptic receptor mechanisms. Pharmacol Biochem Behav 43:697–704

    Article  CAS  PubMed  Google Scholar 

  • Frawley PJ, Smith JW (1992) One-year follow-up after multimodal inpatient treatment for cocaine and methamphetamine dependencies. J Subst Abuse Treat 9:271–286

    Article  CAS  PubMed  Google Scholar 

  • Grove RN, Schuster CR (1982) Suppression of cocaine self-administration by extinction and punishment. Pharmacol Biochem Behav 2:199–208

    Article  Google Scholar 

  • Howard JL, Rohrbach KW, Pollard GT (1982) Cumulative dose–effect curves in a conflict test with incremental shock. Psychopharmacology 78:195–196

    CAS  PubMed  Google Scholar 

  • Johanson CE (1977) The effects of electric shock on responding maintained by cocaine injections in a choice procedure in the rhesus monkey. Psychopharmacology 53:277–282

    CAS  PubMed  Google Scholar 

  • Johanson CE, Schuster CR (1986) The effects of Ro 15-1788 on anxiolytic self-administration in the rhesus monkey. Pharmacol Biochem Behav 24:855–859

    Article  CAS  PubMed  Google Scholar 

  • Kelleher RT, Morse WH (1964) Escape behavior and punished behavior. Fed Proc 23:808–817

    CAS  PubMed  Google Scholar 

  • Kelleher RT, Morse WH (1968) Determinants of the specificity of behavioral effects of drugs. Ergeb Physiol 60:1–56

    CAS  PubMed  Google Scholar 

  • Klingemann HK (1991) The motivation for change from problem alcohol and heroin use. Br J Addict 86:727–744

    CAS  PubMed  Google Scholar 

  • McMillan DE, Hardwick WC, deCosta BR, Rice KC (1991) Effects of drugs that bind to PCP and sigma receptors on punished responding. J Pharmacol Exp Ther 258:1015–1018

    CAS  PubMed  Google Scholar 

  • Miczek KA, Lau P (1975) Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats. Psychopharmacologia 42:263–269

    CAS  PubMed  Google Scholar 

  • Morris MD, Tremmel F, Gebhart GF (1974) Forebrain noradrenaline depletion blocks the release by chlordiazepoxide of behavioral extinction in the rat. Neurosci Lett 12:343–348

    Article  Google Scholar 

  • Panlilio LV, Thorndike EB, Schindler CW (2003) Reinstatement of punishment-suppressed opioid self-administration in rats: an alternative model of relapse to drug abuse. Psychopharmacology 168:229–235

    Article  CAS  PubMed  Google Scholar 

  • Porter JH, Wiley JL, Balster RL (1989) Effects of phencyclidine-like drugs on punished behavior in rats. J Pharmacol Exp Ther 248:997–1002

    CAS  PubMed  Google Scholar 

  • Shaham Y, Erb S, Stewart J (2000) Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res Brain Res Rev 33:13–33

    CAS  PubMed  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20

    Article  CAS  PubMed  Google Scholar 

  • Slikker W Jr, Brocco MJ, Killam KF Jr (1984) Reinstatement of responding maintained by cocaine or thiamylal. J Pharmacol Exp Ther 228:43–52

    CAS  PubMed  Google Scholar 

  • Smith SG, Davis WM (1974) Punishment of amphetamine and morphine self-administration behavior. Psychol Rec 24:477–480

    Google Scholar 

  • Vogel RA, Frye GD, Wilson JH, Kuhn CM, Koepke KM, Mailman RB, Mueller RA, Breese GR (1980) Attenuation of the effects of punishment by ethanol: comparisons with chlordiazepoxide. Psychopharmacology 71:123–129

    CAS  PubMed  Google Scholar 

  • Walker B, Ettenberg A (2001) Benzodiazepine modulation of opiate reward. Exp Clin Psychopharmacol 9:191–197

    Article  CAS  PubMed  Google Scholar 

  • Walker BM, Ettenberg A (2003) The effects of alprazolam on conditioned place preferences produced by intravenous heroin. Pharmacol Biochem Behav 75:75–80

    Article  CAS  PubMed  Google Scholar 

  • Weerts EM, Griffiths RR (2003) The adenosine receptor antagonist CGS15943 reinstates cocaine-seeking behavior and maintains self-administration in baboons. Psychopharmacology 168:155–163

    Article  CAS  PubMed  Google Scholar 

  • Witkin JM, Barrett JE (1976) Effects of pentobarbital on punished behavior at different shock intensities. Pharmacol Biochem Behav 5:535–538

    Article  CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA

    Leigh V. Panlilio, Eric B. Thorndike & Charles W. Schindler

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  1. Leigh V. Panlilio
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  2. Eric B. Thorndike
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  3. Charles W. Schindler
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Correspondence to Leigh V. Panlilio.

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Panlilio, L.V., Thorndike, E.B. & Schindler, C.W. Lorazepam reinstates punishment-suppressed remifentanil self-administration in rats. Psychopharmacology 179, 374–382 (2005). https://doi.org/10.1007/s00213-004-2040-2

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  • DOI: https://doi.org/10.1007/s00213-004-2040-2

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