Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity

Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

doi:10.1007/s00213-015-4157-x

Cited by 86 publications

(54 citation statements)

References 72 publications

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“…Therefore, it is possible that the change in input resistance was primarily due to a modulation of intrinsic K ϩ or Na ϩ /Ca 2ϩ currents at the dendritic/ somatic level. Interestingly, similar adaptations have been observed in the NAc of obesity-prone rats that consume more food (Oginsky et al, 2016). It is tempting to speculate that the increase in the relative excitability of GFPϩ neurons represents a potential mechanism to promote "normal" adaptive and "out-of-control" appetitive and consummatory behaviors by increasing the sensitivity to reward-associated cues.…”

Section: Investigating Neuronal Excitability In the Fos-gfp Mouse: Mementioning

confidence: 59%

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

et al. 2017

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Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFPϩ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFPϩ neurons were more excitable than surrounding GFPϪ neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell.

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Section: Investigating Neuronal Excitability In the Fos-gfp Mouse: Mementioning

confidence: 59%

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

et al. 2017

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“…Sprague Dawley rats were given junk-food using an approach that leads to obesity in some rats (Junk-Food Gainers) but not others (Junk-Food Non-Gainers; Robinson et al , 2015; Oginsky et al , 2016). We then measured the response to a single cocaine injection (a general readout of mesolimbic function), surface vs intracellular expression of AMPAR subunits, and AMPAR-mediated transmission in the NAc core using whole-cell patch clamping approaches in these two populations.…”

Section: Resultsmentioning

confidence: 99%

“…This statistical method provides an unbiased separation that can be applied uniformly across studies (MacQueen, 1967). In addition, we have determined that this is an optimal time point for reliably identifying subpopulations (Robinson et al , 2015; Oginsky et al , 2016; unpublished observations).…”

Section: Methodsmentioning

confidence: 99%

“…), followed 1 h later by cocaine (15 mg/kg, i.p.). This dose was chosen based on previous dose–response studies (Oginsky et al , 2016; Ferrario et al , 2005). …”

Section: Methodsmentioning

confidence: 99%

“…Although it is difficult to address the role of susceptibility in humans, studies in rats have shown that diet-induced alterations in mesolimbic systems and motivation are more pronounced in obesity-susceptible vs - resistant rats (Geiger et al , 2008; Vollbrecht et al , 2016; Robinson et al , 2015; Valenza et al , 2015; Oginsky et al , 2016). Thus recent data suggest that consumption of ‘junk-foods' may produce distinct neural alterations in susceptible vs resistant populations.…”

Section: Introductionmentioning

confidence: 99%

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Eating ‘Junk-Food’ Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

Oginsky

Goforth

Nobile

et al. 2016

Neuropsychopharmacol

135

113

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Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after ‘junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by ‘junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general ‘read out' of mesolimbic function after ‘junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a ‘junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating ‘junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after ‘junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction.

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Pre‐existing differences and diet‐induced alterations in striatal dopamine systems of obesity‐prone rats

Vollbrecht

Mabrouk

Nelson

et al. 2016

Obesity

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Objective Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2/D3 dopamine receptor-mediated transmission prior to and after consumption of “junk-foods” in obesity-prone and obesity-resistant rats. Methods Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2/D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Results Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. Conclusions These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals.

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Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity

Cited by 86 publications

References 72 publications

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

Eating ‘Junk-Food’ Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

Pre‐existing differences and diet‐induced alterations in striatal dopamine systems of obesity‐prone rats

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