Involvement of cholinergic mechanisms in the behavioral effects of dietary fat consumption

Abstract

Clinical reports suggest a positive association between fat consumption and the incidence of hyperactivity, impulsivity and cognitive abnormalities. To investigate possible mechanisms underlying these disturbances under short-term conditions, we examined in Sprague-Dawley rats the influence of 7-day consumption of a high-fat diet (HFD) compared to chow on anxiety, novelty-seeking and exploratory behaviors and also on acetylcholine (ACh) neurotransmission that may mediate these behaviors. The HFD consumption, which elevated circulating fatty acids but produced no change in caloric intake or body weight, stimulated novelty-seeking and exploration in an open field, while reducing anxiety in an elevated plus maze. Using the Ellman assay to measure ACh esterase (AChE) activity that breaks down ACh, the second experiment showed HFD consumption to significantly reduce AChE activity in the frontal cortex, hypothalamus and midbrain. With measurements of [125I]-epibatidine or [125I]-bungarotoxin binding to nicotinic ACh receptors (nAChRs) containing β2 or α7 subunits, respectively, the results also showed HFD consumption to increase both β2-nAChR binding in the medial prefrontal cortex and substantia nigra and α7-nAChR binding in the lateral and ventromedial hypothalamus. When treated with an acute dose of the nicotinic antagonist, mecamylamine (0.5 mg/kg, sc), the HFD animals responded with significantly reduced exploratory and novelty-seeking behaviors, whereas the chow-consuming rats exhibited no response. These findings suggest that the exploratory and novelty-seeking behaviors induced by dietary fat may be mediated by enhanced nicotinic cholinergic activity, which is accompanied by increased density of β2-nAChRs in cortical and midbrain regions associated with impulsivity and locomotor activity and of α7-nAChRs in hypothalamic regions associated with arousal and energy balance.

Western-style diet induces insulin insensitivity and hyperactivity in adolescent male rats

“…Spending increased time in the relatively exposed central portion of the open field is associated with impulsivity [23], as well as reduced levels of thigmotaxis and anxiety [38]. The findings of the current study concur with increased exploration and reduced anxiety observed in male rats consuming a high-fat diet for one week [39]. Similar anxiolytic effects have been documented in both male and female rats fed a cafeteria-style diet for 8 weeks; however, the cafeteria diet reduced distance traveled in the open field [40].…”

Impaired glucose tolerance after streptozotocin microinjection into the mediodorsal prefrontal cortex of the rat

“…It takes place supposedly using complex control mechanisms, in part also determined by the existing multiple functional morphological interrelationships of these structures. The significance of these data is further underlined by the results of recent experiments revealing that high-fat/ cholesterol diet increases plasma TG, total cholesterol, non-HDL, and HDL cholesterol levels in rodents with a subsequent activation of cholinergic processes within the PFC, along with cognitive impairments (23,25), or by demonstrating the causal role of mdPFC D1 dopamine receptors in modifying high-fat food seeking (28). It is already a textbook material that decreased TG can be due to hepatic failure, but our metabolic data -physiological level of cholesterol and lactate dehydrogenase (LDH) -do not indicate liver failure.…”

“…Despite the recent emerging of scarce and indirect data in the literature (23,25,28), little is known yet about the involvement of prefrontal cortical neurons in the central metabolic control.…”

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

“…Also, maternal consumption of a fat-rich diet and being overweight during pregnancy (Dietz, 1998; Hannon, Rao, & Arslanian, 2005), which increase later consumption of and preference for fatty foods in the offspring (Fisher & Birch, 1995), is found to program other behaviors, such as anxiety, novelty seeking, and depression, which themselves are likely to promote drug use and increase vulnerability to drug abuse later in life (Bilbo & Tsang, 2010; Morganstern, Ye, Liang, Fagan, & Leibowitz, 2012; Rizzo, Silverman, Metzger, & Cho, 1997). Similar findings have been obtained in animal studies, demonstrating that in utero exposure to a fat-rich diet increases both alcohol drinking (Bocarsly et al, 2012; Cabanes, de Assis, Gustafsson, & Hilakivi-Clarke, 2000) and nicotine self-administration and seeking (Morganstern et al, 2013), while also promoting the consumption of and responding for palatable foods (Chang, Gaysinskaya, Karatayev, & Leibowitz, 2008; Naef et al, 2011; Ong & Muhlhausler, 2011).…”