Treatment of Substance Use Disorders

Rat intravenous self-administration studies play a critical role in drug abuse liability testing as they evaluate the reinforcing effects of drugs and provide a measure of the motivational or drug-seeking properties of compounds in man. Thus, rats will self-administer drugs that are rewarding in man such as heroin, cocaine and nicotine.

 

Drug abuse is an enormous public health issue. The efficacy of novel treatments for substance use disorders can be determined using the rat intravenous self-administration procedure. The test drug is given repeatedly once robust operant responding to the positive reinforcer has been established and its effects on various aspects of the intravenous administration of the drug of abuse are investigated:

  • Fixed ratio schedules of reinforcement can be used to evaluate whether the test drug can reduce the number of injections, the total intake or the rate of self-administration of the drug of abuse.
  • Progressive ratio schedules of reinforcement can be used to assess whether the test drug can reduce the breakpoint for reinforcement of the drug of abuse.

 

We have validated the model using the mu-opioid agonist, remifentanil, and buprenorphine, a mu-opioid partial agonist, which is an established substitution therapy for opioid addiction.

 

Repeated administration of buprenorphine significantly reduced the
breakpoint of remifentanil in rats on a PR schedule of reinforcement

 

Repeated Administration of Buprenorphine Significantly Reduced the Breakpoint of Remifentanil in Rats on a PR Schedule of Reinforcement

 

Prevention of relapse is essential for the successful treatment of substance use disorders. Drug-seeking behaviour can be triggered by re-exposure to the drug or to environmental cues associated with drug-taking. Intravenous self-administration can also be used to investigate drug-primed and/or cue-induced reinstatement of drug-seeking behaviour in rats. We have validated this model of relapse to drug-seeking behaviour using cocaine and heroin.

 

Active lever presses during drug primed and/or cue
induced reinstatement of heroin seeking behavior

 

Active lever presses during drug primed and/or cue induced reinstatement of heroin seeking behavior

 

Active lever presses during drug primed and/or cue
inducement reinstatement of cocaine seeking behavior

 

Active lever presses during drug primed and/or cue induced reinstatement of cocaine seeking behavior

 

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