Effects of environmental manipulations on cocaine-vs-social choice in male and female rats

Abstract

Cocaine use disorder occurs in an environment where cocaine and other nondrug commodities are concurrently available. Preclinical drug-vs-nondrug choice procedures are one simplified method of modeling this complex clinical environment. The present study established a discrete-trial cocaine-vs-social interaction choice procedure in male and female rats and determined sensitivity of choice behavior to manipulations of reinforcer magnitude and non-contingent "sample" reinforcer presentation. Rats could make up to nine discrete choices between an intravenous cocaine infusion (0.1-1.0 mg/kg/inf) and social interaction with a same-sex social "Partner" rat. Cocaine infusions were available under a progressive-ratio (PR) schedule of reinforcement, and social interaction was available under a fixed-ratio (FR) 3 schedule. Social interaction was chosen over no or small cocaine doses (saline, 0.01 mg/kg/inf) and behavior was reallocated away from social and towards cocaine at larger cocaine doses (1.0 mg/kg/inf). Manipulating social interaction time as one method to alter social reinforcer magnitude did not significantly alter cocaine-vs-social choice. Removing the non-contingent reinforcer presentations before the discrete choice trials also failed to affect cocaine-vs-social choice, suggesting the time interval was sufficient to minimize any potential influence of the non-contingent cocaine infusions on subsequent choice behavior. Overall, the present results were consistent with previous drug-vs-social choice studies and extend our knowledge of environmental factors impacting drug-vs-social choice. Future studies determining the pharmacological sensitivity of cocaine-vs-social choice will be important in expanding the preclinical utility of these procedures for candidate medication drug development.

Keywords: Addiction; Choice; Cocaine; Progressive ratio; Self-administration; Social interaction.

Figure 1.

Effect of cocaine dose on cocaine-vs.-social interaction choice. Top panels: (A) percent cocaine choice as a function of cocaine dose. (B) trials completed for cocaine (PR 3, 6, 10, 18, 32, 56, 100, 180, 320), completed for social interaction (FR3), or omitted as a function of cocaine dose. All points represent the mean ± SEM for the final 2 days of testing. Filled points denote statistical significance (p < 0.05) relative to saline; symbols represent significant (p < 0.05) comparisons within a dose: *difference from the other reinforcer and omitted trials; ^#difference from omitted trials only. Bottom panels: Individual subject behavioral allocation on the final day of testing between cocaine (red), social interaction (black), or omitted trials (white) when the alternative to social interaction was 0.1 mg/kg/inf cocaine (C) or 1.0 mg/kg/inf cocaine (D). Each row corresponds to a single subject, and each column corresponds to a discrete choice trial. Results depicted are representative of one testing day. n = 5 (2M/3F) for saline, n = 6 (2M/4F) for 0.10 mg/kg/inf cocaine, n = 5 (2M/3F) for 0.32 mg/kg/inf, and n = 7 (3M/4F) for 1.0 mg/kg/inf cocaine.

Figure 2.

Cocaine-vs-social interaction choice across testing days. Abscissae: testing day. Ordinates: number of trials completed for cocaine, completed for social interaction, or omitted within a session. All points and bars represent the mean ± SEM. Lines represent main effect of Reinforcer (p < 0.05); Symbols represent significant (p < 0.05) post-hoc comparisons: ^$difference between cocaine, social, and omitted; *difference from the other reinforcer and omitted; ^%difference between social and omitted; ^#Difference from omitted trials only. n = 2–5 (2M/3F) for saline, n = 4–6 (2M/4F) for 0.1 mg/kg/inf cocaine, n = 3–5 (2M/3F) for 0.32 mg/kg/inf cocaine, and n = 6–7 (3M/4F) for 1.0 mg/kg/inf cocaine dose.

Figure 3.

Effect of increasing social interaction duration on cocaine-vs-social choice. (A) Percent cocaine choice between 1.0 mg/kg/inf cocaine and 30-s or 60-s social interaction. Points represent individual subject means for the final 2 days of testing; bars represent group means. (B) number of trials completed for each reinforcer or omitted across testing days. Points and bars represent the daily mean ± SEM. Lines represent main effect of Reinforcer; ^#difference from omitted trials only (p < 0.05) (C, D) Individual subject behavioral allocation on the final day of testing between cocaine (red), social interaction (black), or omitted trials (white) when the alternative to cocaine was 30-s (C) or 60-s social interaction (D)

Figure 4.

Effect of removing social interaction on cocaine-vs-social choice. (A) Percent cocaine choice between 0.32 mg/kg/inf cocaine and 30-s or 0-s social interaction. Points represent individual subject means for the final 2 days of testing; bars represent group means. (B) number of trials completed for each reinforcer or omitted across testing days. Points and bars represent the daily mean ± SEM. (C, D) Individual subject behavioral allocation on the final day of testing between cocaine (red), social interaction (black), or omitted trials (white) when the alternative to cocaine is 30-s (C) or 0-s social interaction (D)

Figure 5.

Effect of eliminating non-contingent reinforcer presentation on cocaine-vs-social choice. (A) Percent cocaine choice between 1.0 mg/kg/inf cocaine and 30 s social interaction with and without non-contingent cocaine and social presentation during the pre-choice sampling period of each daily session. Points represent individual subject means for the final 2 days of testing; bars represent group means. (B) number of trials completed for each reinforcer or omitted across testing days. Points and bars represent the daily mean ± SEM. Bars represent main effect of Reinforcer; ^#difference from omitted trials only (p < 0.05) (C, D) Individual subject behavioral allocation on the final day of testing between cocaine (red), social interaction (black), or omitted trials (white) with (C) or without non-contingent reinforcer presentation (D)