Eating High Fat Chow Decreases Dopamine Clearance in Adolescent and Adult Male Rats but Selectively Enhances the Locomotor Stimulating Effects of Cocaine in Adolescents

Abstract

Background:Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats.Methods:Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow).Results:Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow.Conclusions:These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine.

Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity

“…2a). This is consistent with a recent report showing that exposure to either unlimited or restricted high-fat food (35% fat) did not alter the induction of cocaine-induced locomotor sensitization (Baladi et al 2015). However, these data are in contrast to cross-sensitization between high-fat diets and amphetamines where methamphetamine-induced sensitization is enhanced during high-fat diet exposure (McGuire et al 2011; Robinson et al 2015).…”

“…Specifically, cocaine blocks the DAT, preventing the removal of dopamine that is released through normal membrane depolarization; whereas amphetamine causes reverse transport of dopamine through the DAT, regardless of normal dopamine release. High-fat diets, insulin and leptin (which are increased by obesity) can all alter DAT function (Baladi et al 2015; Daws et al 2011; Figlewicz et al 1994; Perry et al 2010). Thus, enhanced induction of locomotor sensitization in response to amphetamine, but not cocaine, after diet-induced obesity may be due to the effects of diet manipulation on DAT function and the enhancement of amphetamine’s ability to reverse transport dopamine through the DAT, but do not alter cocaine’s effects on DAT blockade.…”

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

“…Acute administration of insulin enhances DAT activity and expression, whereas rats made hypoinsulinemic (e.g., via pharmacological agents or feeding conditions) have decreased DAT activity and expression (Figlewicz et al, 1994;Patterson et al, 1998;Carvelli et al, 2002;Owens et al, 2005;Sevak et al, 2008). Moreover, manipulating insulin levels (pharmacologically or via feeding conditions) can decrease AMPH-induced DA efflux through DAT (Williams et al, 2007) and can dramatically alter the behavioral effects of drugs acting at DAT, such as cocaine and METH (McGuire et al, 2011;Baladi et al, 2012Baladi et al, , 2015.…”

Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats

“…For example, eating high fat chow increases yawning induced by direct-acting dopamine receptor agonists (i.e., quinpirole; Baladi et al, 2011b; Baladi and France, 2010). Similarly, eating high fat chow enhances the sensitivity of rats to cocaine-induced locomotion and sensitization (Baladi et al, 2012b, 2015). Females are more sensitive than males to cocaine (Anker and Carroll, 2011; Lynch and Carroll, 1999; Chin et al, 2001) and the impact of eating high fat chow on sensitivity to cocaine is greater in females than in males (Baladi et al, 2015, 2011; Serafine et al, 2014b) and is more dramatic in adolescent rats compared with adults (Baladi et al, 2012b, 2015).…”

“…Insulin signaling can impact dopamine systems (Daws et al, 2011); for example, dopamine transporter expression and function are decreased in obese rats and in rats that are insulin resistant (Narayanswami et al, 2013; Owens et al, 2012; South and Huang, 2008; Speed et al, 2011; Williams et al, 2007). However, enhanced sensitivity to drugs acting on dopamine systems occurs even in the absence of diet-induced obesity (see Baladi et al, 2012b, 2015) and insulin resistance (Serafine et al, 2014a). Thus, eating a high fat diet in the absence of obesity or insulin resistance is sufficient to alter sensitivity to drugs.…”