Wistar rats choose alcohol over social interaction in a discrete-choice model

Abstract

Animal models of substance use disorders have been criticized for their limited translation. One important factor behind seeking and taking that has so far been largely overlooked is the availability of alternative non-drug rewards. We recently reported that only about 15% of outbred Wistar rats will choose alcohol over a sweet solution of saccharin. It was also shown using a novel operant model of choice of drugs over social rewards that social interaction consistently attenuates self-administration and incubation of craving for stimulants and opioids. Whether this is also true for alcohol and choice of alcohol over a sweet reward translates to social rewards is currently unknown. We therefore evaluated choice between alcohol and a social reward in different experimental settings in both male and female Wistar rats. We found, in contrast to prior work that employed discrete choice of drugs vs. social reward, that rats almost exclusively prefer alcohol over social interaction, irrespective of the nature of the social partner (cagemate vs. novel rat), the length of interaction, housing conditions and sex. Alcohol choice was reduced when the response requirement for alcohol was increased. However, rats persisted in choosing alcohol, even when the effort required to obtain it was 10-16 times higher (for females and males respectively) than the one for the social reward. Altogether, these results indicate that the social choice model may not generalize to alcohol, pointing to the possibility that specific interactions between alcohol and social reward, not seen when a sweet solution is used as an alternative to the drug, may play a crucial role in alcohol vs. social choice experiments.

Fig. 1. Rats prefer alcohol over social interaction with a cagemate, independently of the duration of the interaction.

A Experimental Timeline for experiment 1 (B): Total number of active lever presses for the social reinforcer and alcohol across sessions. Tukey’s post-hoc comparisons: ***p < 0.001: significant differences compared with lever presses for social reward (C): Total number of reinforcers earned during sessions. Tukey’s post-hoc comparisons: ***p < 0.001: significant differences compared with the total number of earned social rewards (D): Percentage of alcohol choice across sessions using a discrete choice procedure. E Individual distribution of rats. B–D Data are expressed as mean ± SEM.

Fig. 2. Rats choose alcohol over social interaction, even with a novel rat, regardless of housing conditions.

A Total number of active lever presses for the social reinforcer in group housed and chronic isolation rats. B Total number of social reinforcers earned. C Mean breakpoint recorded during the progressive ratio sessions of reinforcement. Tukey’s post-hoc comparisons: ***p < 0.001 as significant differences compared with breakpoints for social reward. D Mean number of samplings displayed by group housed and chronically isolated rats for both alcohol and the social reinforcer. Tukey’s post-hoc comparisons: ***p < 0.001 and **p < 0.01 as significant differences compared with samplings for social reward. E Percentage of alcohol choice. F Individual distribution of grouped and chronically isolated rats. G Percentage of alcohol choice across sessions when increasing the fixed ratio. H Number of earned reinforcers (alcohol and social) across sessions when increasing the fixed ratio. I Percentage of completed trials across increased fix ratio requirement sessions. Data of (A–E) and (G–I) is expressed as mean ± SEM.

Fig. 3. Social interaction functions as a reinforcer in chronically isolated rats.

A, B Total number of social reinforcers earned in the group housed rats and chronic isolation rats respectively. C Total number of active lever presses for the social reinforcer in the group housed and chronic isolation rats. D–G Percentage of social choice vs. water in the group housed rats and chronic isolation rats respectively. E–H Number of earned reinforcers (water and social) across sessions earned in the group housed rats and chronic isolation rats respectively. F–I Percentage of completed trials across sessions in the group housed rats and chronic isolation rats respectively. Data of (A–I) is expressed as mean ± SEM.

Fig. 4. Effect of manipulating alcohol concentrations on social choice.

A–C Percentage of social choice across sessions when increasing the % of alcohol and the length of the inter-trial in the group housed rats and chronic isolation rats respectively. B–E Number of earned reinforcers (alcohol and social) across sessions when increasing the % of alcohol and the length of the inter-trial in the group housed rats and chronic isolation rats respectively. C–F Percentage of completed trials across sessions when increasing the % of alcohol and the length of the inter-trial in the group housed rats and chronic isolation rats respectively. Data of (A–F) is expressed as mean ± SEM.

Fig. 5. Sex differences in motivation for social reward and social choice.

A Total number of active lever presses to get alcohol and the social reinforcer of male and female rats. B Total number of reinforcers earned. C Mean breakpoint recorded during the progressive ratio sessions of reinforcement. Tukey post-hoc comparisons: ***p < 0.001 as significant difference compared with breakpoints for social reward for males. **p < 0.001 as significant difference compared with breakpoints for alcohol expressed by for females. D Mean number of samplings displayed by male and female rats for both alcohol and the social reinforcer. Tukey post-hoc comparisons: ***p < 0.001 as significant difference compared with samplings for social reward for males. **p < 0.001 as significant difference compared with samplings for alcohol expressed by for females. E Percentage of alcohol choice. F Individual distribution of male and female rats. G Percentage of alcohol choice across sessions when increasing the fixed ratio. Tukey post-hoc comparisons: **p < 0.01 and *p < 0.05 as significant difference compared with the percentage of choice showed by females. H Total number of earned reinforcers (alcohol and social) across sessions when increasing the fixed ratio. I Percentage of completed trials across increased fixed ratio requirement sessions. Data of (A–E) and (G–I) is expressed as mean ± SEM.