title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA.
authors.forename: Max F
authors.initials: MF
authors.lastname: Oginsky
authors.affiliation: Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Maust
authors.affiliation: Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Corthell
authors.affiliation: Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, MSRB III 1301, Ann Arbor, MI, 48109, USA. ferrario@umich.edu.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Ferrario
mesh_terms: D000375:Aging; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D005971:Glutamates; D003042:Cocaine
keywords: Cocaine; Excitability; Nucleus accumbens; Obesity; Sensitization; Striatum