Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for saccharin and less avoidance of a cocaine-paired saccharin cue.

Abstract

Rats avoid intake of a saccharin cue when paired with a drug of abuse. While this is true for most subjects, the degree of avoidance of the drug-paired cue depends upon many factors including an individual rat’s preference for rewards. That said, the direction of this effect is complex. For example, reward-preferring Lewis rats exhibit greater cocaine-induced avoidance of a saccharin cue relative to Fischer 344 rats; while reward-preferring mice that over express ΔFosB (NSE-tTA x TetOp-ΔFosB) exhibit less avoidance of the drug-paired taste cue compared to controls. The aim here was to use two strains of commonly used mice, C57BL/6J and DBA/2J, to determine whether known differences in sensitivity to rewards will facilitate or attenuate drug-induced suppression of intake of a drug-paired taste cue. The results of Experiment 1 demonstrate that C57BL/6J mice, compared with DBA/2J mice, exhibit attenuated suppression of saccharin intake when it is paired with cocaine. The results of Experiment 2 demonstrate that strain differences in impulsivity are not likely to account for these differences. It is proposed that, while the C57BL/6J mice typically are more responsive to drug, they also are more responsive to natural rewards (in this case saccharin), and the stronger preference for saccharin serves to militate against drug.

Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice

“…The data in the current manuscript demonstrate that ceftriaxone delays acquisition of cocaine-induced suppression in C57BL/6J mice (Figure 2). Published literature of suppression in mice (e.g., Freet et al , 2013, Freet et al , 2014, Freet et al , 2009) demonstrates that saline controls and drug groups start with similar saccharin intake on Trial 1. This makes sense, of course, given that drug (or saline) has yet to be experienced on that trial.…”

“…injection of either saline (n=15/cell) or 30 mg/kg cocaine (n=15/cell). The 30 mg/kg cocaine dose was used in the current study as published data (Freet et al , 2013) indicates that, in C57BL/6J mice at least, it is the minimum dose required for significant suppression of saccharin intake (i.e., 10 and 20 mg/kg are ineffective in this strain). Taste-drug pairings occurred in the morning for 5 trials (Trials 1–5).…”

Cocaine-induced suppression of saccharin intake and morphine modulation of Ca2+ channel currents in sensory neurons of OPRM1 A118G mice

“…The devaluation of alternative rewards observed in addiction can be modeled in rodents when presentation of a saccharin cue elicits anticipation of the availability of a drug of abuse [20, 28, 29]. In this paradigm, saccharin-saline controls continue to consume saccharin over trials, while rats and mice that have had the saccharin cue paired with a drug of abuse (e.g., cocaine or morphine) avoid intake of the same saccharin cue [20, 23]. It is believed that rodents may initially avoid intake of a saccharin cue, at least in part, because they are anticipating the availability of the highly preferred drug of abuse.…”

“…Specifically, we have found that animal models of general reward sensitivity (i.e., increased preference not only for drugs of abuse but for natural rewards as well) exhibit an opposite profile (i.e., lesser suppression of intake of the drug-paired taste cue). This is the case for C57BL/6J mice vs. DBA/2J mice [23] and for NSE-tTA × TetOp-ΔFosB mice, a transgenic mouse strain with inducible elevations of the transcription factor ΔFosB [38]. Finally, female Sprague- Dawley rats are known to take more drug and to work harder for drug than males [39– 41], but when access to cocaine is preceded by brief access to a sweet, female Sprague-Dawley rats ingest more of the saccharin cue and take less drug than their male counterparts [42].…”

“…The dose of cocaine increased over trials (trials 1–4: 20 mg/kg, trials 5–7: 40 mg/kg, trials 8–11: 60 mg/kg). Escalating, repeated cocaine is a common within-subject preparation used in our laboratory; the 20 mg/kg dose is below that required to produce suppression (the minimum required dose in mice similar to the A118G background strain is 30 mg/kg [23]). Although the 60 mg/kg dose can produce seizure-like activity and elevated locomotor activity when administered acutely, these effects are not observed with the repeated escalating doses used in the current preparation, most likely due to the development of tolerance [24, 25].…”