A quantitative analysis of the effects of qualitatively different reinforcers on fixed ratio responding in inbred strains of mice

Hutsell, Blake A.; Newland, M. Christopher

doi:10.1016/j.nlm.2013.01.005

Cited by 21 publications

(32 citation statements)

References 72 publications

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“…This seemingly contradicts earlier re ports that these strains show aversion to ethanol (Elmer et al, 1987a, 1987b, 1988; Belknap et al, 1993; Boyce-Rustay et al, 2008; Crabbe, 1983; Hutsell & Newland, 2013; Rhodes et al, 2007; Rodgers & McClearn, 1962; Yoneyama et al, 2008). However, earlier operant-based studies have concluded that ethanol acts as a poor reinforcer in BALB (Elmer et al, 1987a, 1987b, 1988), suggesting the response rates observed in the current study may be unrelated to the reinforcing properties of ethanol in this strain.…”

Section: Discussioncontrasting

confidence: 57%

Mouse strain differences in punished ethanol self-administration

Halladay

Kocharian

Holmes

2017

Alcohol

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Determining the neural factors contributing to compulsive behaviors such as alcohol-use disorders (AUDs) has become a significant focus of current preclinical research. Comparison of phenotypic differences across genetically distinct mouse strains provides one approach to identify molecular and genetic factors contributing to compulsive-like behaviors. Here we examine a rodent assay for punished ethanol self-administration in four widely used inbred strains known to differ on ethanol-related behaviors: C57BL/6J (B6), DBA/2J (D2), 129S1/SvImJ (S1), and BALB/cJ (BALB). Mice were trained in an operant task (FR1) to reliably lever-press for 10% ethanol using a sucrose-fading procedure. Once trained, mice received a punishment session in which lever pressing resulted in alternating ethanol reward and footshock, followed by tests to probe the effects of punishment on ethanol self-administration. Results indicated significant strain differences in training performance and punished attenuation of ethanol self-administration. S1 and BALB showed robust attenuation of ethanol self-administration after punishment, whereas behavior in B6 was attenuated only when the punishment and probe tests were conducted in the same contexts. By contrast, D2 were insensitive to punishment regardless of context, despite receiving more shocks during punishment and exhibiting normal footshock reactivity. Additionally, B6, but not D2, reduced operant self-administration when ethanol was devalued with a bitter tastant. B6 and D2 showed devaluation of sucrose self-administration, and punished suppression of sucrose seeking was context dependent in both the strains. While previous studies have demonstrated avoidance of ethanol in D2, particularly when ethanol is orally available from a bottle, current findings suggest this strain may exhibit heightened compulsive-like self-administration of ethanol, although there are credible alternative explanations of the phenotype of this strain. In sum, these findings offer a foundation for future studies examining the neural and genetic factors underlying AUDs.

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Section: Discussioncontrasting

confidence: 57%

Mouse strain differences in punished ethanol self-administration

Halladay

Kocharian

Holmes

2017

Alcohol

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“…This could influence responding in a strain-dependent fashion. In support of this perspective, both BALB/c and C57BL/6 mice can inhibit responding according to fixed ratio schedules of reinforcement that progressively increase from 15 to 45, 90, 180, 360, and ultimately 590 over the course of several days (Hutsell and Newland, 2013), while the rapid and un-signaled modification in response-outcome contingencies here resulted in considerable strain differences. We suggest that the uncertainty engendered by instrumental contingency degradation or even the constantly changing response requirements of a within-session progressive ratio response schedule, rather than simply differences in extinction conditioning, stimulate responding in BALB/c mice and contribute to strain differences.…”

Section: Discussionmentioning

confidence: 73%

“…This suggests that food is uniquely reinforcing for BALB/c mice, particularly under the conditions of pronounced food restriction — e.g. , such that body weights during testing fall to 85% of initial body weight (Deroche et al, 1997;Johnson et al, 2009;Johnson et al, 2010) and/or when the reinforcer is highly palatable (sucrose pellets or sweet liquid) (Hutsell and Newland, 2013). Variability in stress and anxiety systems, along with the ostensibly higher value placed on food reinforcement by BALB/c mice (see also figure 3h), could dramatically affect food-reinforced instrumental decision making.…”

Section: Discussionmentioning

confidence: 99%

Strain commonalities and differences in response-outcome decision making in mice

Zimmermann

Hsu

Gourley

2016

Neurobiology of Learning and Memory

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The ability to select between actions that are more vs. less likely to be reinforced is necessary for survival and navigation of a changing environment. A task termed “response-outcome contingency degradation” can be used in the laboratory to determine whether rodents behave according to such goal-directed response strategies. In one iteration of this task, rodents are trained to perform two food-reinforced behaviors, then the predictive relationship between one instrumental response and the associated outcome is modified by providing the reinforcer associated with that response non-contingently. During a subsequent probe test, animals can select between the two trained responses. Preferential engagement of the behavior most likely to be reinforced is considered goal-directed, while non-selective responding is considered a failure in response-outcome conditioning, or “habitual.” This test has largely been used with rats, and less so with mice. Here we compiled data collected from several cohorts of mice tested in our lab between 2012-2015. Mice were bred on either a C57BL/6 or predominantly BALB/c strain background. We report that both strains of mice can use information acquired as a result of instrumental contingency degradation training to select amongst multiple response options the response most likely to be reinforced. Mice differ, however, during the training sessions when the familiar response-outcome contingency is being violated. BALB/c mice readily generate perseverative or habit-like response strategies when the only available response is unlikely to be reinforced, while C57BL/6 mice more readily inhibit responding. These findings provide evidence of strain differences in response strategies when an anticipated reinforcer is unlikely to be delivered.

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“…This model-comparison analysis has been growing in popularity in the behavioral and neural sciences to model drug and neurotoxicant effects (Avila et al, 2009; Franck, Koffarnus, House, & Bickel, 2015; Sanabria, Acosta, Killeen, Neisewander, & Bizo, 2008) and it has been used in our laboratory for model construction (Hutsell & Newland, 2013). It does not rely on traditional null-hypothesis testing.…”

Section: Methodsmentioning

confidence: 99%

Adolescent methylmercury exposure affects choice and delay discounting in mice

Boomhower

Newland

2016

NeuroToxicology

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The developing fetus is vulnerable to low-level exposure to methylmercury (MeHg), an environmental neurotoxicant, but the consequences of exposure during the adolescent period remain virtually unknown. The current experiments were designed to assess the effects of low-level MeHg exposure during adolescence on delay discounting, preference for small, immediate reinforcers over large, delayed ones, using a mouse model. Thirty-six male C57BL/6n mice were exposed to 0, 0.3, or 3.0 ppm mercury (as MeHg) via drinking water from postnatal day 21 through 59, encompassing the murine adolescent period. As adults, mice lever-pressed for a 0.01-cc droplet of milk solution delivered immediately or four 0.01-cc droplets delivered after a delay. Delays ranged from 1.26 to 70.79 seconds, all presented within a session. A model based on the Generalized Matching Law indicated that sensitivity to reinforcer magnitude was lower for MeHg-exposed mice relative to controls; responding in MeHg-exposed mice was relatively indifferent to the larger reinforcer. Sensitivity to reinforcer delay was reduced (delay discounting was decreased) in the 0.3-ppm group, but not in the 3.0-ppm group, compared to controls. Adolescence is a developmental period during which the brain and behavior may be vulnerable to MeHg exposure. As with gestational exposure, the effects are reflected in the impact of reinforcing stimuli.

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A quantitative analysis of the effects of qualitatively different reinforcers on fixed ratio responding in inbred strains of mice

Cited by 21 publications

References 72 publications

Mouse strain differences in punished ethanol self-administration

Mouse strain differences in punished ethanol self-administration

Strain commonalities and differences in response-outcome decision making in mice

Adolescent methylmercury exposure affects choice and delay discounting in mice

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