Effects of dopamine modulation on chronic stress-induced deficits in reward learning.

Anhedonia is characteristically preceded by chronic stress, likely involving downstream effects of glucocorticoid alterations on dopamine (DA) function. To elucidate the neural underpinnings of this interaction, we examined whether acute pharmacological modulation of DA alters reward learning after chronic mild stress (CMS). Forty-eight male Wistar rats were exposed to a 21-day CMS regime (n = 48 no stress controls) before completing the probabilistic reward task (PRT), a well-validated cross-species test of reward learning. We first examined whether stress-induced reward dysfunction could be restored by systemic injections of low-dose amisulpride (AMI), which increases DA transmission via D2-like autoreceptor blockade. Then, we investigated region-specific effects through bilateral infusions of quinpirole (QUIN), a D2-like receptor agonist, into either the nucleus accumbens core (NAcc) or medial prefrontal cortex (mPFC). Blunted reward learning in CMS animals was reversed by acute AMI administration, but this treatment did not alter reward learning in the no stress group. Elevated adrenal gland weight, a proxy for stress reactivity, predicted lower reward learning in the untreated CMS group. This effect was extinguished following AMI treatment. These findings might be attributed to significantly higher D2 receptor density in the NAcc of high stress reactive animals. To this end, NAcc QUIN infusions potentiated reward learning relative to mPFC QUIN infusions in CMS rats, but there was no effect in no stress control rats. Collectively, these findings suggest that DA modulation reverses stress-induced reward dysfunction, even among the most stress-reactive animals. The effect might depend on D2-like receptor activation in the mesolimbic system.

Binge-like intake of sucrose reduces the rewarding value of sucrose in adult rats.

Binge eating disorder is the most common eating disorder, but its underlying etiology is poorly understood. Both humans and animals exhibit binge-like intake of highly-palatable food, suggesting that the behavior is driven by the rewarding properties of food, rather than homeostatic signals. Food reward is regulated, in part, by endogenous opioid mechanisms which, themselves, may be altered by excessive eating. We examined this hypothesis by testing whether binge-like sucrose intake modifies the subsequent development of a conditioned place preference (CPP) to sucrose and morphine in both female and male adult rats. Separate groups were given intermittent (12h) or continuous (24 h) access to a sweet solution (10% sucrose or 0.1% saccharin) and food in their home cage over 28 days. Intermittent sucrose access induced binge-like intake, defined as increased consumption within the first hour; importantly, daily sucrose intake was similar for continuous and intermittent access groups. In a later test, all rats developed a conditioned place preference (CPP) to 15% sucrose with the exception of female and male rats given 12-h intermittent access to sucrose. In a separate experiment, all groups displayed a CPP to morphine (4 mg/kg). These findings demonstrate that binge-like sucrose intake, not just increased consumption, disrupts reward processing without affecting stimulus-reward learning. This fits with clinical evidence of hypo-reward responsivity in patients with binge eating disorder.