Neuroadaptations in the Striatal Proteome of the Rat Following Prolonged Excessive Sucrose Intake

Abstract

Obesity is a contemporary health problem of rapidly increasing prevalence. One possible cause of obesity is loss of control over consumption of highly palatable foodstuffs, perhaps mirroring the processes involved in drug addiction. Accordingly, the striatum may be a key neural substrate involved in both food and drug craving. We hypothesised here that prolonged exposure to 10% sucrose solution might cause neuroadaptations in the striatum that are analogous to those previously reported following prolonged exposure to alcohol or recreational drugs. Male Wistar rats were given constant access to 10% sucrose solution (in addition to normal lab chow and tap water) for 8 months and were compared with control rats receiving no sucrose access. Rats in the sucrose group typically drank more than 100 ml of sucrose solution per day and showed 13% greater body weight than controls at the end of the 8 months. Striatal dopamine (DA) concentrations were decreased in the sucrose group rats relative to controls. Differential expression of 18 proteins was identified in the striatum of the sucrose group rats relative to controls. Down regulated proteins included pyridoxal phosphate phosphatase, involved in DA synthesis, and glutathione transferase, involved in free radical scavenging. Up regulated proteins included prolactin (which is under negative regulation by DA) and adipose differentiation-related protein, involved in fat synthesis. We hypothesise that DA-related neuroadaptations in the striatum caused by prolonged sucrose intake may partly drive compulsive intake and seeking of high palatability foodstuffs, in a similar way to that observed with drug and alcohol addictions.

Psychological and Neurobiological Correlates of Food Addiction

“…Proponents of the concept suggest that similarities between FA and other substance addictions, in particular, operant conditioning, effects of mood and stress, cue reactivity, craving, and impulsivity support food as an addictive substance (Ahmed et al, 2014; Berenson et al, 2015; Frayn et al, 2016; Kishinevsky et al, 2012; Pelchat et al, 2004). There is also some neural evidence supporting food as an addiction because of observations of downregulation of reward circuitry and difficulties with top-down cognitive control (Blum et al, 2014; Stice, Spoor, Bohon, et al, 2008; Volkow et al, 2003, 1997).…”

“…Over time, the consumption of highly palatable foods may lead to neuroadaptations in brain reward centers involving the downregulation of D2 receptors, as seen in other substance addictions: motivation switches to a desire to ameliorate negative emotional or physiological states, such as depression, anxiety, irritability, or other somatic symptoms related to absence of the highly palatable food (de Macedo et al, 2016; Meule & Kubler, 2012; Parylak et al, 2011). To date, most of the evidence for this type of neuroplasticity in FA comes from animal studies (Ahmed et al, 2014; Johnson & Kenny, 2010; van de Giessen et al, 2013). …”

Mesolimbic dopamine and its neuromodulators in obesity and binge eating

“…Diet-induced obesity is associated with decreased tyrosine hydroxylase (TH) expression, the rate-limiting factor in the synthesis of dopamine in dopamine-relevant brain regions. [13][14][15] Furthermore, blunted striatal dopamine concentrations in diet-induced obesity have been described using several techniques, including total dopamine concentrations and/or dopamine turnover in the striatum in brain punches, 16,17 decreased extracellular concentrations measured with microdialysis, 18,19 and decreased evoked release with electrochemistry. 18 Only one study revealed an increase in nucleus accumbens dopamine measured with microdialysis in obesity prone rats on an 8-week high fat diet.…”

Recent studies of the effects of sugars on brain systems involved in energy balance and reward: Relevance to low calorie sweeteners

“…One such study observed decreased striatal DA concentrations following prolonged access to a sucrose solution in high-sucrose drinking rats [36], a finding also reported by this group in response to chronic exposure to ethanol [37]. Expression of tyrosine hydroxylase (TH), an enzyme involved in DA synthesis, was also decreased in the striatum of high sucrose-drinking rats.…”