Lorazepam reinstates punishment-suppressed remifentanil self-administration in rats

Psychopharmacology (Berl). 2005 May;179(2):374-82. doi: 10.1007/s00213-004-2040-2. Epub 2004 Oct 27.


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 anti-punishment 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 microg/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 anti-punishment effects of both abused drugs and therapeutic agents in the treatment of individuals with a history of drug abuse.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Electroshock
  • Extinction, Psychological / drug effects
  • Heroin / pharmacology
  • Heroin Dependence / psychology
  • Lorazepam / pharmacology*
  • Male
  • Piperidines / pharmacology*
  • Punishment*
  • Rats
  • Rats, Sprague-Dawley
  • Remifentanil
  • Self Administration
  • Substance-Related Disorders / psychology*


  • Analgesics, Opioid
  • Anti-Anxiety Agents
  • Piperidines
  • Heroin
  • Lorazepam
  • Remifentanil