Social odor choice buffers drug craving

Abstract

Social interactions are rewarding and protective against substance use disorders, but it is unclear which specific aspect of the complex sensory social experience drives these effects. Here, we investigated the role of olfactory sensory experience on social interaction, social preference over cocaine, and cocaine craving in rats. First, we conducted bulbectomy on both male and female rats to evaluate the necessity of olfactory system experience on the acquisition and maintenance of volitional social interaction. Next, we assessed the effect of bulbectomy on rats given a choice between social interaction and cocaine. Finally, we evaluated the influence of olfactory sensory experience by training rats on volitional partner-associated odors, assessing their preference for partner odors over cocaine to achieve voluntary abstinence and assessing its effect on the incubation of cocaine craving. Bulbectomy impaired operant social interaction without affecting food and cocaine self-administration. Rats with intact olfactory systems preferred social interaction over cocaine, while rats with impaired olfactory sense showed a preference for cocaine. Providing access to a partner odor in a choice procedure led to cocaine abstinence, preventing incubation of cocaine craving, in contrast to forced abstinence or non-contingent exposure to cocaine and partner odors. Our data suggests the olfactory sensory experience is necessary and sufficient for volitional social reward. Furthermore, the active preference for partner odors over cocaine buffers drug craving. Based on these findings, translational research should explore the use of social sensory-based treatments utilizing odor-focused foundations for individuals with substance use disorders.

Fig. 1. Olfactory sensory system is critical for acquisition of volitional social interaction.

A Timeline of the experiment. B Food self-administration. Number of food (2 h) rewards over 5 sessions. C Social self-administration. Left: Representative pictures of sham and bulbectomy surgery; scale bar = 5 mm. Right: Number of social (2 h) rewards over 10 sessions. D Food self-administration during social training. Number of food (2 h) rewards over 2 additional food sessions during social self-administration. Sham group (black) n = 10 (5 males, 5 females); bulbectomy group (red) n = 9 (5 males, 4 females). Data are mean ± SEM. F = food session during social self-administration training. See also Supplementary S1A.

Fig. 2. Olfactory sensory system is critical for maintenance of volitional social interaction.

A Timeline of the experiment. B Food self-administration. Number of food (2 h) rewards over 5 sessions. C Social self-administration. Left: Number of social (2 h) rewards over 8 sessions prior surgery. Middle: Representative pictures of sham and bulbectomy surgery; scale bar = 5 mm. Right: Number of social (2 h) rewards over 10 sessions after surgery. D Food self-administration during social training. Number of food (2 h) rewards over 2 additional food sessions during social self-administration. Sham group (black) n = 7 (4 males, 3 females); bulbectomy group (red) n = 6 (4 males, 2 females). Data are mean ± SEM. F = food session during social self-administration training. See also Supplementary  S1B.

Fig. 3. Olfactory sensory system is critical for social preference.

A Timeline of the experiment. B Food self-administration. Number of food (2 h) rewards over 5 sessions. C Social self-administration. Left: Representative pictures of sham and bulbectomy surgery; scale bar = 5 mm. Right: Number of social (2 h) rewards over 8 sessions. D Cocaine self-administration. Number of cocaine (6 h) infusions over 10 sessions. E Choice. Average preference score (number of social rewards/[number of social reward + number of drug infusions]). 0 indicates preference for cocaine; 1 indicates preference for social reward. Sham group (black) n = 17 (10 males, 7 females); bulbectomy group (red) n = 9 (4 males, 5 females). Data are mean ± SEM. See also Supplementary  S1C.

Fig. 4. Social odors mediate volitional social reward.

A Timeline of the experiment. B Food self-administration. Number of food (2 h) rewards over 5 sessions. C Odor self-administration. Left: Number of urine odor (2 h) rewards over 5 sessions. Right: Number of full odor (2 h) rewards over 5 sessions. No odor group (black) n = 8 (4 males, 4 females); odor group (red) n = 8 (4 males, 4 females). D Own odor self-administration. Number of odor (2 h) rewards over 5 sessions; n = 6 (4 males, 2 females). E Opposite-sex odor self-administration. Number of odor (2 h) rewards over 5 sessions; n = 5 (3 males, 2 females). Data are mean ± SEM.

Fig. 5. Active odor preference prevents incubation of cocaine craving.

A Timeline of the experiment. B Left: Odor self-administration. Number of odor (2 h) rewards over 5 sessions. Right: Cocaine self-administration. Number of cocaine (6 h) rewards over 12 sessions. C Voluntary abstinence. Left: Average preference score (number of odor rewards / [number of odor reward + number of cocaine infusions]). Right: Individual data for preference scores: closed circles depict rats’ behavior used to yoke the deliveries of cocaine and odors for the non-contingent group, while open circles represent preference scores for the active choice group. 0 indicates preference for cocaine; 1 indicates preference for odor reward over 10 sessions. D Incubation test. Active-lever presses during the 30-min test sessions. During testing, active-lever presses led to contingent presentation of the light cue previously paired with cocaine infusions during training, but not cocaine or odor delivery or exposure (extinction conditions). * Different from active lever on test day 1. # Different from active lever from the active-choice voluntary abstinence group on test day 15. Active-choice voluntary abstinence n = 14 (12 males, 2 females); non-contingent abstinence n = 7 (4 males, 3 females); Forced abstinence n = 12 (10 males, 2 females). Data are mean ± SEM.