EFFECTS OF NEGATIVE CONSEQUENCES ON DRUG SELF ADMINISTRATION IN RATS
RICHARDS, JERRY B Principal Investigator
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DESCRIPTION (provided by applicant): The primary objective of the proposed research is to develop a rodent model of self administration (SA) in which drug consumption has delayed negative consequences. Self administration procedures in which the animals make responses that are reinforced by IV drug injections are widely used and are perhaps the most convincing non-human animal models of drug abuse. Non-human animal SA models, however, may not model important aspects of human drug SA. In humans, impulsivity is considered an important component of drug abuse because individuals take drugs despite the knowledge of negative (often delayed) outcomes associated with drug use. In contrast, standard laboratory animal models of SA have no explicit negative outcomes associated with the SA of the drug. Because there are currently no SA models that incorporate negative consequences, the impact of negative outcomes is not generally incorporated into current ideas about the underlying behavioral and neurobiological mechanisms mediating drug abuse. The goal of the Experiment 1 of this application is to determine a dose of cocaine and an amount of water that have equivalent reinforcing efficacy. In this application reinforcing efficacy is measured using progressive ratio schedules of reinforcement. In progressive ratio schedules, reinforcement efficacy is operationally defined as the break point (BP) which indicates the maximum number of responses an animal will make on a progressive ratio schedule of reinforcement for a given reinforcer. Determination of a dose of cocaine and an amount of water that have equivalent efficacy will insure that cocaine and water reinforcers of equivalent reinforcing efficacy are used In Experiments 2 and 3. Experiment 2 will determine if immediate shock has different effects on the reinforcing efficacy of drug and natural reinforcers using the progressive ratio schedule of reinforcement. Building upon Experiments 1 and 2, Experiment 3 will determine the effects of delaying the shock on the reinforcing efficacy of the cocaine/shock and water/shock reinforcers. These studies will advance to our understanding of drug abuse by determining if punishment or delays to punishment have similar (or dissimilar) effects on drug (cocaine) and natural (water) reinforcers of equivalent reinforcing efficacy. These results will help to determine if a 'punished' SA model is a valuable tool with which to investigate the behavioral and cognitive regulation of drug abuse by negative consequences. PUBLIC HEALTH RELEVANCE: The primary objective of the proposed research is to develop a rodent model of self administration (SA) in which drug consumption has delayed negative consequences. There is little doubt that non-human animal SA procedures model important aspects of drug taking in humans; however in some respects the typical application of this model in the laboratory does not model important aspects of drug consumption by human addicts. According to the Diagnostic and Statistical Manual of Mental Disorders (APA, 1994) an important characteristics of human drug addiction is continued drug intake despite harmful consequences. However, current non human animal models of drug abuse do not address this important issue. Consequently, the impact of negative outcomes is not generally incorporated into current ideas about the underlying behavioral and neurobiological mechanisms mediating drug abuse. We believe that drug abuse in humans is a function of two separate processes, 'rewarding' positive affective responses to the drug and 'impulsivity-related' factors, or influences that normally inhibit or limit the use of drugs. Development of a non human SA model that incorporates negative consequences will enhance research into 'impulsivity-related factors' that are necessary for drug abstinence.