Reward sensitivity deficits in a rat model of compulsive eating behavior

Abstract

Compulsive eating behavior is hypothesized to be driven in part by reward deficits likely due to neuroadaptations to the mesolimbic dopamine (DA) system. Therefore, the aim of this study was to assess deficits in reward system functioning and mesolimbic DA after alternating a standard chow with palatable diet, a model of compulsive eating. In this model, rats in the control group (Chow/Chow) are provided a standard chow diet 7 days a week, while the experimental group (Chow/Palatable) is provided chow for 5 days a week ("C Phase"), followed by 2 days of access to a highly palatable sucrose diet ("P Phase"). We first tested the sensitivity to d-Amphetamine's stimulatory, reward-enhancing, and primary rewarding effects using a locomotor activity assay, an intracranial self-stimulation (ICSS) procedure, and a conditioned place preference test, respectively. We then quantified DA release in the nucleus accumbens (NAc) shell after treatment with d-Amphetamine using in vivo microdialysis, quantified levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA using quantitative polymerase chain reaction (qPCR), and lastly, quantified baseline extracellular DA and function of DAT in vivo using quantitative "no-net-flux" microdialysis. Chow/Palatable rats displayed blunted d-Amphetamine-induced locomotor activity, insensitivity to d-Amphetamine potentiation of ICSS threshold, and decreased place preference for d-Amphetamine during the P Phase. We found that Chow/Palatable rats had blunted DA efflux following d-Amphetamine treatment. Furthermore, DAT mRNA was increased in Chow/Palatable rats during the P Phase. Finally, quantitative "no-net-flux" microdialysis revealed reduced extracellular baseline DA and DAT function in Chow/Palatable rats. Altogether, these results provide evidence of reduced reward system functioning and related neuroadaptations in the DA and DAT systems in this model of compulsive eating. Reward deficits, resulting from repeated overeating, may in turn contribute to the perpetuation of compulsive eating behavior.

Bacteroides uniformis CECT 7771 Modulates the Brain Reward Response to Reduce Binge Eating and Anxiety-Like Behavior in Rat

“…Among other causes, desensitization is due, in part, to a lower release of dopamine in the NAc and a reduced D2R density. This process typically occurs in drug addiction; however, a similar situation seems to pertain to palatable food, which can lead to an eating disorder [ 2 , 14 , 50 – 52 ]. We observed that rats subjected to IF show low levels of extracellular dopamine but increase their chow and drink intake (stimulus) during the binge period, possibly to achieve the same level of satisfaction.…”

Withdrawal from Extended, Intermittent Access to A Highly Palatable Diet Impairs Hippocampal Memory Function and Neurogenesis: Effects of Memantine

“…Moreover, it has been shown that a gender difference in spatial navigation exists, with women typically performing worse than males [55,56]. Although the animal model of diet alternation used here has been developed in both female and male rats, no direct sex comparisons have ever been performed [15,16,[20][21][22][23]. Future studies will be important to make direct comparisons between sexes in the consummatory, stress-related, learning and memory outcomes following this diet alternation procedure.…”

Antagonism of Sigma‐1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice

“…In order to confirm that any behavioral effects seen were not confounded by potential stimulatory or sedative effects of BD‐1063, effects of BD‐1063 on locomotor activity were examined using an Opto‐M3 activity system (Columbus Instruments, Columbus, OH) as reported previously (Dore et al, 2013; Iemolo et al, 2016; Moore et al, 2020). The same animals used in the ethanol drinking test were used for locomotor activity, after 4 further weeks of undisturbed drinking (see Figure 1).…”