Overexpression of ΔFosB is associated with attenuated cocaine-induced suppression of saccharin intake in mice.

Freet, Christopher S.; Steffen, Cathy; Nestler, Eric J.; Grigson, Patricia S.

doi:10.1037/a0015033

Cited by 12 publications

(18 citation statements)

References 77 publications

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“…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.…”

Section: Discussionmentioning

confidence: 97%

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

Freet

Lawrence

2015

Physiology & Behavior

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Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200 mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1 hour and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24 hours for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice.

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Section: Discussionmentioning

confidence: 97%

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

Freet

Lawrence

2015

Physiology & Behavior

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“…For example, similar to Lewis rats, transgenic NSE-tTA x TetOp-ΔFosB mice with selective over expression of the transcription factor ΔFosB, demonstrate an increase in the perceived rewarding value of drugs of abuse (Nestler, Barrot, & Self, 2001; Nestler, Kelz, & Chen, 1999). However, unlike Lewis rats, cocaine-induced suppression of intake of a saccharin cue is attenuated compared with controls (Freet, Steffen, Nestler, & Grigson, 2009). These mice also exhibit an increased preference for sweets and for a running wheel (Freet et al , 2009; Werme et al , 2002).…”

Section: Introductionmentioning

confidence: 99%

“…However, unlike Lewis rats, cocaine-induced suppression of intake of a saccharin cue is attenuated compared with controls (Freet, Steffen, Nestler, & Grigson, 2009). These mice also exhibit an increased preference for sweets and for a running wheel (Freet et al , 2009; Werme et al , 2002). Thus, we have hypothesized that, a general increased preference for all rewards in these mice, as opposed to a specific increased preference for drugs serves to attenuate the suppressive effect of the drug on intake of the saccharin cue.…”

Section: Introductionmentioning

confidence: 99%

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

Freet

Arndt

Grigson

2013

Behavioral Neuroscience

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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.

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“…Avoidance of the heroin-paired saccharin cue also was not associated with a reduction in WLS, as previously found (Tacelosky et al, 2015), but it was associated with an elevation in both β-catenin and NCS-1 in the PFC. The reduction in ALB and the failure to find reduced levels of WLS in the PFC in high ALB rats are not likely due to small differences in the behavioral methodology used here vs. other papers (e.g., Deroche-Gamonet et al, 2004; Tacelosky et al, 2015), but it may relate to the use of a different antibody for WLS or to the fact that the rats in this study had prior exposure to a sweet, which can be highly protective (Cason and Grigson, 2013; Freet et al, 2009; Grigson and Hajnal, 2007; Lenoir et al, 2013). Future studies will test whether these proteins differ early in training, prior to differences in drug exposure, and whether ALB can be reduced by relatively brief prior exposure to a sweet.…”

Section: Discussionmentioning

confidence: 74%

Early avoidance of a heroin-paired taste-cue and subsequent addiction-like behavior in rats

Jenney

Petko

Ebersole

et al. 2016

Brain Research Bulletin

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The ability to predict individual vulnerability to substance abuse would allow for a better understanding of the progression of the disease and development of better methods for prevention and/or early intervention. Here we use drug-induced devaluation of a saccharin cue in an effort to predict later addiction-like behavior in a model akin to that used by Deroche-Gamonet et al. (2004) and seek to link such vulnerability to changes in expression of various mu opioid receptor and D2 receptor-interacting proteins in brain. The results show that the greatest heroin-induced suppression of intake of a saccharin cue is associated with the greatest vulnerability to later addiction-like behavior and to differences in the expression of WLS, β-catenin, and NCS-1 in brain compared to rats that exhibited the least suppression of intake of the heroin-paired cue and/or saline controls. Finally, because the self-administration model employed produced no significant differences in drug intake between groups, overall, the resultant changes in protein expression can be more closely linked to individual differences in motivation for drug.

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Overexpression of ΔFosB is associated with attenuated cocaine-induced suppression of saccharin intake in mice.

Abstract: Rodents suppress intake of saccharin when it is paired with a drug of abuse

Cited by 12 publications

References 77 publications

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

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

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

Early avoidance of a heroin-paired taste-cue and subsequent addiction-like behavior in rats

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