Eating “junk food” has opposite effects on intrinsic excitability of nucleus accumbens core neurons in obesity-susceptible versus -resistant rats

Abstract

The nucleus accumbens (NAc) plays critical roles in motivated behaviors, including food seeking and feeding. Differences in NAc function contribute to overeating that drives obesity, but the underlying mechanisms are poorly understood. In addition, there is a fair degree of variation in individual susceptibility versus resistance to obesity that is due in part to differences in NAc function. For example, using selectively bred obesity-prone and obesity-resistant rats, we have found that excitability of medium spiny neurons (MSNs) within the NAc core is enhanced in obesity-prone versus -resistant populations, before any diet manipulation. However, it is unknown whether consumption of sugary, fatty “junk food” alters MSN excitability. Here whole cell patch-clamp recordings were conducted to examine MSN intrinsic excitability in adult male obesity-prone and obesity-resistant rats with and without exposure to a sugary, fatty junk food diet. We replicated our initial finding that basal excitability is enhanced in obesity-prone versus obesity-resistant rats and determined that this is due to a lower fast transient potassium current ( IA) in prone versus resistant groups. In addition, the junk food diet had opposite effects on excitability in obesity-prone versus obesity-resistant rats. Specifically, junk food enhanced excitability in MSNs of obesity-resistant rats; this was mediated by a reduction in IA. In contrast, junk food reduced excitability in MSNs from obesity-prone rats; this was mediated by an increase in inward-rectifying potassium current. Thus individual differences in obesity susceptibility influence both basal excitability and how MSN excitability adapts to junk food consumption. NEW & NOTEWORTHY Medium spiny neurons (MSNs) in the nucleus accumbens of obesity-prone rats are hyperexcitable compared with MSNs from obesity-resistant rats. We found that 10 days of “junk food” exposure reduces MSN excitability in obesity-prone rats by increasing inward-rectifying potassium current and increases MSN excitability in obesity-resistant rats by decreasing fast transient potassium current. These data show that there are basal and junk food diet-induced differences in MSN excitability in obesity-prone and obesity-resistant individuals; this may contribute to previously observed differences in incentive motivation.

Metaplasticity in the ventral pallidum as a potential marker for the development of diet-induced obesity

“…For example, the expression of the inhibitory D2 dopamine receptor is decreased both in obese humans (9) and animal models of obesity (6,10). Also, the excitatory input to the NAc is stronger in obese rats (14,15). Both these findings point to a possible increase in the activity of NAc GABAergic VPprojecting neurons in obesity.…”

“…Differences in long-term plasticity between OP and OR mice may be innate 7 In this and previous works, we and others showed various synaptic and physiological parameters in the NAc and the VP that differ between OP and OR animals (14,15). For obvious reasons, slice recordings in all these studies could only be performed after the HFHS diet and splitting mice to OP and OR groups.…”

“…Previous studies showed that not only does weight gain correlate with addiction-like behaviors towards palatable food (14,15,20), it also correlates with synaptic changes in the NAc (14, 15) -OP rats show stronger excitatory input to the NAc compared to OR rats. As the VP is a major target of the NAc, we expect that the physiology of the VP will also differ between OP and OR mice.…”

“…Mice were eventually tested at the end of the HFHS diet on a progressive ratio task (where the number of lever presses required to obtain a pellet increased progressively). Progressive ratio schedule was 5,9,12,15,20,25,32,40,50,62,77,95,118,145,178,219,268,328,402,492 and 603 lever presses per pellet. The test was terminated after 6 hours or if the mouse did not progress to the next level within one hour of achieving the previous one.…”

“…Research so far has indeed shown obesity-related changes both in the function of the reward system and in motivation-driven food seeking behavior. Thus, the expression level of the dopamine receptor D2/3 in the striatum is decreased in obese humans (7)(8)(9) and rodents (6,10); opioid signaling in both the ventral tegmental area (VTA) (11,12), and the nucleus accumbens (NAc) (12,13) is altered in obese rodents; and the glutamatergic input to the NAc is potentiated in rats that develop diet-induced obesity (14,15), akin to the effect seen after withdrawal from cocaine (16,17) or nicotine (16,18). Possibly as a consequence of these changes in the reward system, rats and mice that gain the most weight in a diet-induced obesity model also show the highest motivation to obtain palatable food (10,14,(19)(20)(21).…”