Pre‐existing differences and diet‐induced alterations in striatal dopamine systems of obesity‐prone rats

Abstract

Objective Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2/D3 dopamine receptor-mediated transmission prior to and after consumption of “junk-foods” in obesity-prone and obesity-resistant rats. Methods Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2/D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Results Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. Conclusions These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals.

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

“…3). This is consistent with our earlier study using a single dose of cocaine (Vollbrecht et al In Press). Thus, obesity-prone rats are sensitized compared to their obesity-resistant counterparts.…”

“…We next examined intrinsic excitability of MSNs in the NAc core of obesity-prone and -resistant rats because there are basal differences in dopamine systems in obesity-prone vs. -resistant rats, dopamine-mediated transmission strongly influences MSN excitability, and cocaine sensitization is associated with alterations in intrinsic excitability, (Geiger et al 2008; Hu 2007; Kourrich et al 2015; Kourrich and Thomas 2009; Marinelli et al 2006; Rada et al 2010; Valenza et al 2015; Vollbrecht et al In Press). Recordings were made from adult and adolescent obesity-prone and obesity-resistant rats without diet manipulation or cocaine exposure (Fig.…”

“…Glutamatergic transmission provides the main excitatory drive to MSNs, whereas dopamine-mediated transmission can powerfully modulate excitability of MSNs; thus, the convergence of these inputs in the NAc can ultimately drive cue-triggered motivational responses (Everitt and Wolf 2002; Kelley 2004; Perez et al 2006). Although, basal differences in striatal dopamine levels, and mesolimbic dopamine receptor expression and function have been found (Geiger et al 2008; Geiger et al 2009; Rada et al 2010; Valenza et al 2015; Vollbrecht et al In Press; Vollbrecht et al 2015) no previous studies have examined basal differences in neurotransmission to MSNs in the NAc core of obesity-prone and obesity-resistant rats.…”

Eating ‘Junk-Food’ Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

“…Although it is difficult to address the role of susceptibility in humans, studies in rats have shown that diet-induced alterations in mesolimbic systems and motivation are more pronounced in obesity-susceptible vs - resistant rats (Geiger et al , 2008; Vollbrecht et al , 2016; Robinson et al , 2015; Valenza et al , 2015; Oginsky et al , 2016). Thus recent data suggest that consumption of ‘junk-foods' may produce distinct neural alterations in susceptible vs resistant populations.…”

“…Although informative, this model requires the induction of weight gain and diet manipulation in order to identify susceptible populations. Thus we also examined the effects of junk-food in rats selectively bred for their propensity or resistance to diet-induced obesity (Levin et al , 1997; Vollbrecht et al , 2015, 2016). …”