RenaSci

Treatment of Substance Use Disorders

Operant Chambers for Self-administration Studies

 

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

Buprenorphine Significantly Reduced the Number of Injections of Remifentanil taken by Rats on a FR2 Schedule of Reinforcement

Buprenorphine Significantly Reduced the Number of Injections of Remifentanil taken by Rats on a PR Schedule of Reinforcement

 

The intravenous self-administration procedure can also be used to examine the effects of novel treatments on relapse to drug-seeking behaviour.

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.

We have developed an intravenous self-administration procedure to investigate drug-primed and/or cue-induced reinstatement of drug-seeking behaviour in rats. Rats were trained to self-administer cocaine on a FR5 schedule in daily 2 hour tests (acquisition). All cocaine infusions were paired with contingent cues (tone/light). Responding was then extinguished on saline in the absence of the cues (extinction). Following the drug abstinence period, rats were tested in 4 once-daily 2 hour reinstatement sessions. Rats were presented with a single bolus of cocaine (drug-priming) plus the tone/light (contingent) cues, cocaine or the tone/light cues alone. Active lever presses were measured on a FR5 schedule with rats receiving saline infusions. 

Rat Model of Relapse to Drug-seeking Behaviour

Rat Model of Relapse to Drug-seeking Behaviour

 

All interventions induced reinstatement of active lever pressing (cocaine-seeking behaviour). The effects of drug-priming and tone/light were additive. The drug plus the tone/light cues significantly increased responding across all four reinstatement sessions. The drug or cues alone gave an increase on responding in the first reinstatement session.

The technique can be used to evaluate the potential of novel drugs to prevent relapse to drug-seeking behaviour in substance use disorders. 

Studies can be performed in rats trained to self-administer cocaine, heroin or nicotine.

Please contact us for further information about our preclinical models for assessing the ability of novel drugs to treat substance use disorders.