Max F Oginsky1, Joel D Maust1, John T Corthell1, Carrie R Ferrario2. 1. Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA. 2. Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA. ferrario@umich.edu.
Abstract
RATIONALE: Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. OBJECTIVES: We examined differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity and basal differences in striatal neuron function in adult and in adolescent obesity-prone and obesity-resistant rats. METHODS: Susceptible and resistant outbred rats were identified based on "junk-food" diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine-induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). RESULTS: In rats that became obese after eating junk-food, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ∼60 % at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. CONCLUSIONS: Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals, and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats.
RATIONALE: Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to humanobesity; these differences may be more pronounced in susceptible populations. OBJECTIVES: We examined differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity and basal differences in striatal neuron function in adult and in adolescent obesity-prone and obesity-resistant rats. METHODS: Susceptible and resistant outbred rats were identified based on "junk-food" diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine-induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). RESULTS: In rats that became obese after eating junk-food, the expression of locomotor sensitization was enhanced compared to non-obeserats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ∼60 % at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. CONCLUSIONS: Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals, and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats.
Authors: Carrie R Ferrario; Jessica A Loweth; Mike Milovanovic; Kerstin A Ford; Gregorio L Galiñanes; Li-Jun Heng; Kuei Y Tseng; Marina E Wolf Journal: Neuropharmacology Date: 2011-01-27 Impact factor: 5.250
Authors: Carrie R Ferrario; Xuan Li; Xiaoting Wang; Jeremy M Reimers; Jamie L Uejima; Marina E Wolf Journal: Neuropsychopharmacology Date: 2009-11-18 Impact factor: 7.853
Authors: Peter J Vollbrecht; Omar S Mabrouk; Andrew D Nelson; Robert T Kennedy; Carrie R Ferrario Journal: Obesity (Silver Spring) Date: 2016-02-05 Impact factor: 5.002
Authors: Peter J Vollbrecht; Kathryn M Nesbitt; Omar S Mabrouk; Aaron M Chadderdon; Emily M Jutkiewicz; Robert T Kennedy; Carrie R Ferrario Journal: Behav Brain Res Date: 2017-11-09 Impact factor: 3.332
Authors: Ana-Clara Bobadilla; Constanza Garcia-Keller; Jasper A Heinsbroek; Michael D Scofield; Victoria Chareunsouk; Cara Monforton; Peter W Kalivas Journal: Neuropsychopharmacology Date: 2017-07-20 Impact factor: 7.853
Authors: Marie A Labouesse; Andrea M Sartori; Oliver Weinmann; Eleanor H Simpson; Christoph Kellendonk; Ulrike Weber-Stadlbauer Journal: Proc Natl Acad Sci U S A Date: 2018-09-25 Impact factor: 11.205