Food Restriction Increases Glutamate Receptor-Mediated Burst Firing of Dopamine Neurons

Abstract

Restriction of food intake increases the acquisition of drug abuse behavior and enhances the reinforcing efficacy of those drugs. However, the neurophysiological mechanisms responsible for the interactions between feeding state and drug use are largely unknown. Here we show that chronic mild food restriction increases the burst firing of dopamine neurons in the substantia nigra. Dopamine neurons from food-restricted mice exhibited increased burst firing in vivo, an effect that was enhanced by an injection of the psychomotor stimulant cocaine (10 mg/kg, i.p.). Food restriction also enhanced aspartic acid-induced burst firing of dopamine neurons in an ex vivo brain slice preparation, consistent with an adaptation occurring in the somatodendritic compartment and independent of a circuit mechanism. Enhanced burst firing persisted after 10 d of free feeding following chronic food restriction but was not observed following a single overnight fast. Whole-cell patch-clamp recordings indicated that food restriction also increased electrically evoked AMPAR/NMDAR ratios and increased D2 autoreceptor-mediated desensitization in dopamine neurons. These results identify dopamine neurons in the substantia nigra as a convergence point for the interactions between feeding state and drugs of abuse. Furthermore, increased glutamate transmission combined with decreased autoreceptor inhibition could work in concert to enhance drug efficacy in response to food restriction.

Nucleus accumbens core dopamine signaling tracks the need‐based motivational value of food‐paired cues

“…This finding is seemingly inconsistent with recent evidence that NAc shell, but not NAc core cue-evoked dopamine release is attenuated by within-session satiety (Saddoris et al 2015), though the amount of food consumed by rats in this study was only a fraction of that consumed during the satiety treatment here. These findings do, however, accord well with those showing that dopamine neuron burst firing (Branch et al 2013) and food-evoked NAc dopamine release (Cone et al 2014) are attenuated by satiety and findings that NAc phasic dopamine responses are greater to cues predictive of a nutritive versus non-nutritive palatable reward (McCutcheon et al 2012, Beeler et al 2012 ). Satiety has also been shown to attenuate dopamine efflux measured with microdialysis in food-rewarded tasks (Ahn & Phillips 1999, Ostlund et al 2011).…”

Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms

“…Since VTA DA signaling modifies the motivation to work for food rewards (e.g. “wanting”), but not their hedonic value (“liking”) or ad lib food consumption (Berridge et al, 2010; Salamone and Correa, 2012), we speculated that LHA Nts neurons might selectively modulate working for food and/or feeding in an energy-restricted state (Ahn and Phillips, 1999; Branch et al, 2013). To test this, we fasted Nts Cre ;NtsR1 ++ and Nts Cre ;NtsR1 KOKO mice overnight and activated LHA Nts neurons upon restoration of chow the following morning.…”

“…LHA Nts neurons are, however, linked with the VTA DA system (Patterson et al, 2015) that modifies the motivation to obtain food rewards (Berridge et al, 2010) and food necessary for survival. For example, the changes in circulating ghrelin and leptin during food-deprivation modulate VTA DA signaling to increase the motivation to eat and restore energy balance (Branch et al, 2013; Larder and O’Rahilly, 2012; Wilson et al, 1995). Anorectic signals thus more profoundly diminish feeding in fasted animals with an elevated drive to eat; for example, exogenous leptin treatment more effectively reduces food intake in fasted vs. fed rodents (Ahima et al, 1996; Sharma et al, 2012).…”

Role of Dopamine Neurons in Reward and Aversion: A Synaptic Plasticity Perspective

“…The overall idea is that food restriction can enhance motivational or hedonic states that are important for learning and acquisition of behavioral tasks. Surprisingly, animals under food restriction protocols display not just an increase in behavioral responses to drugs of abuse, but also enhanced burst firing of DA neurons, increased AMPA/NMDA ratio and D2 autoreceptor-mediated desensitization in DA neurons (Branch et al, 2013).…”