Drug specificity in drug versus food choice in male rats

Abstract

Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

Figure 1. Cocaine and Heroin Self-administration

Mean number (±SEM) of infusions self-administered over the last 10 self-administration sessions with Drug 1 and Drug 2. Sessions lasted 3 hours or until 50 infusions were earned. Rats were run for a minimum of 10 self- administration sessions and until the number of infusions consumed on the last 2 days was within 30% of the average of those 2 days. One rat required 13 sessions when heroin was Drug 1. One rat required 12 sessions when cocaine was Drug 2.

Figure 2. Cocaine and Heroin Preference

Mean percentage (±SEM) of free choice trials (14 per session) on which drug was chosen in preference to food, over the last five choice sessions with Drug 1 and Drug 2. One rat completed 13 of 14 free choice trials on one session, otherwise, all rats completed all trials on all sessions (i.e., 0% = 0/14 trials, 50% = 7/14 trials, 100% = 14/14 trials). Rats were run for a minimum of five sessions and until there was no change greater than 20% in the percentage of trials on which the drug was chosen, across the final two sessions (for three rats choosing between cocaine and food, this was relaxed to a change no greater than 50% over three sessions). One rat required nine sessions when cocaine was Drug 1. Individual preferences are also shown (average of last two choice sessions).

Figure 3. Individual Subjects’ Preference across Drugs

Individual subjects’ preference for both cocaine and heroin relative to food. Each point in the scatterplot represents the percentage of free choice trials (14 per session; one rat completed 13 of 14 trials on one session, all others completed 14 of 14 on all sessions) on which an individual chose each drug in the presence of a food alternative (averaged over the last two choice sessions). Also presented is a regression line with 95% confidence limits (R² = 0.05, p = 0.39)