Stimulus Complexity and Mouse Strain Drive Escalation of Operant Sensation Seeking Within and Across Sessions in C57BL/6J and DBA/2J Mice

Abstract

Sensation seeking is a heritable trait that is genetically correlated with substance use; the shared genetic mechanisms underlying these traits are largely unknown. The relationship of sensation seeking and substance use has practical importance because discovering genes that drive sensation seeking can reveal genes driving substance use, and quantification of sensation seeking in mice is higher throughput and less technically challenging than quantification of volitional drug use. In order to fully understand the genetic mechanisms driving sensation seeking, it is critical to first understand the nongenetic factors driving sensation seeking. In the present study, we used the operant sensation seeking paradigm to assess the effects of stimulus complexity on sensation seeking in C57BL/6J and DBA/2J mice. These strains are the founders of the BXD recombinant inbred mouse panel which enables the discovery of genes driving phenotypic variation. This study led to four principal conclusions. First, all sensory stimuli used in the study, regardless of complexity or number of stimulus modalities, served as reinforcers for C57BL/6J and DBA/2J mice. Second, for both C57BL/6J and DBA/2J mice, sensation seeking for a high complexity sensory stimulus was significantly greater than sensation seeking for a low complexity sensory stimulus. Third, for both C57BL/6J and DBA/2J mice, sensation seeking escalated significantly within-session when a multimodal sensory stimulus of medium or high complexity was used but not when a unimodal sensory stimulus of low complexity was used. Finally, both the magnitude of sensation seeking and the magnitude of within-session escalation of sensation seeking were significantly greater in mice from the DBA/2J strain relative to mice from the C57BL/6J strain. Collectively, these findings indicate that stimulus complexity and genetic background drive escalation of operant sensation seeking within and across sessions, and that the BXD recombinant inbred mouse panel can be used to discover the genetic mechanisms underlying these phenomena.

Strain and sex dependent effects of isolation housing relative to environmental enrichment on operant sensation seeking in mice

“…The increased active lever pressing observed in DBA/2J mice is unlikely to be secondary to increased locomotion because of significantly lower open field locomotion in DBA/2J relative to C57BL/6J 11 . Our findings in this study replicate our findings from a previous study in which DBA/2J mice selfadministered more sensory stimuli than C57BL/6J mice on an FR-1 schedule 18 . Collectively, our data from this study and our previous study investigating OSS in mice indicate that DBA/2J mice are higher sensation seekers on the OSS paradigm relative to C57BL/6J mice.…”

“…Thus, although sensation seeking was greater in female mice from some BXD strains in that study, the specific BXD strains tested resulted in overall greater sensation seeking in male mice. www.nature.com/scientificreports/ Collectively, operant sensation seeking data from this experiment and our previous two operant sensation seeking experiments 9,18 indicate the following. First, environmental enrichment facilitates learning in operant conditioning paradigms as indicated by greater lever dissociation in enriched mice.…”

“…The equipment used in the present study has been described in detail previously 18 . Briefly, OSS data were collected using Med Associates operant conditioning chambers enclosed in sound attenuating cubicles.…”

Extreme phenotypic diversity in operant response to intravenous cocaine or saline infusion in the hybrid mouse diversity panel

“…In both infusate groups, activation of the active lever triggers a potentially perceptible intravenous infusion and a flashing house light; it is possible that either serves as a reinforcer or affects behavioural arousal. Similar discrete light stimuli were sufficient to reinforce instrumental actions in the BXD population, and this trait demonstrated heritability 36,37 . However, active lever preference was lower in the saline group in the present study, so reinforcement due to perceptible cues after an active lever press may not be a prominent motivator of responding for saline infusions.…”

Extreme Phenotypic Diversity in Operant Responding for an Intravenous Cocaine or Saline Infusion in the Hybrid Mouse Diversity Panel

“…In both infusate groups, activation of the active lever triggers a potentially perceptible infusion and a flashing house light; it is possible that the light stimulus serves as a reinforcer. Similar discrete light stimuli were sufficient to reinforce instrumental actions in the BXD population, and this trait demonstrated heritability (Dickson et al, 2015; Dickson & Mittleman, 2020). However, if the light stimulus served as an effective reinforcer in our procedure, a preference for the active lever that produces it would be expected but was not observed here.…”