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A High Fat Diet Reduces Dopamine Terminal Function and Increases Behavioral Sensitization to Amphetamine in C57BL/6 Mice

Steve C. Fordahl,Sara R. Jones-2015-04-01-The FASEB Journal
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TL;DRAbstract

High fat (HF) diet-induced obesity has been shown to have a profound impact on neurobiological health, and has been associated with neurodegenerative and addictive disorders involving the mesolimbic dopamine system. Little is known as to how HF alters dopamine neurotransmission, so we used fast scan cyclic voltammetry and behavioral pharmacology to identify dopamine terminal changes that occur in the nucleus accumbens (NAc) of C57BL/6 mice after six-week access to a HF diet. Mice with unrestricted access to HF (60% kcals from fat) gained significantly more weight than chow fed controls (34.5 g and 25.9 g, respectively; p < 0.0001), and exhibited increased behavioral sensitivity to repeated amphetamine (AMPH) administration compared to chow fed mice (p < 0.0001). Baseline evoked dopamine release in the NAc was comparable between chow and HF (0.86 and 1.07 μM, respectively), and baseline Vmax was unaltered by HF (chow: 1.63 μM/s; HF: 1.74 μM/s). A history of AMPH exposure, however, signi

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High fat (HF) diet-induced obesity has been shown to have a profound impact on neurobiological health, and has been associated with neurodegenerative and addictive disorders involving the mesolimbic dopamine system. Little is known as to how HF alters dopamine neurotransmission, so we used fast scan cyclic voltammetry and behavioral pharmacology to identify dopamine terminal changes that occur in the nucleus accumbens (NAc) of C57BL/6 mice after six-week access to a HF diet. Mice with unrestricted access to HF (60% kcals from fat) gained significantly more weight than chow fed controls (34.5 g and 25.9 g, respectively; p < 0.0001), and exhibited increased behavioral sensitivity to repeated amphetamine (AMPH) administration compared to chow fed mice (p < 0.0001). Baseline evoked dopamine release in the NAc was comparable between chow and HF (0.86 and 1.07 μM, respectively), and baseline Vmax was unaltered by HF (chow: 1.63 μM/s; HF: 1.74 μM/s). A history of AMPH exposure, however, signi

Keywords

Nucleus accumbensDopamineInternal medicineEndocrinologyAmphetamineAutoreceptorReuptakeChemistry

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