Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism

Abstract

Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-hr sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3 h/day × 1 day or 10 days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1 day or 7 days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0 μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7 days, but not 1 day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D1-like receptors during chronic stress may help to prevent future relapse in dieters.

<p>Chronic stress increases susceptibility to food addiction by increasing the levels of DR2 and MOR in the nucleus accumbens</p>

“…Considering the evidence described above, we postulate that stress-coupled food addiction involves different mechanisms. The present study did not detect changes in DR1 levels in the NAc, although a previous study indicated that DR1 is possibly involved in the process of chronic stress. 30 …”

“…29 When repeatedly exposed to a stressor, mice gradually habituated to the stressor and their food consumption was restored. Mice selectively increase their response to palatable food cues following chronic stress. 30 In addition, chronic stress exposure enhances vulnerability to cue-induced relapse.…”

Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism

“…Cocaine and SCH-23390 were dissolved in 0.9% sterile saline. The dose of SCH-23390 was chosen based on our previous work (Ball et al, 2017; Ball et al, 2015; Ball et al, 2016) and the doses of cocaine were chosen based on pilot data. All doses refer to weight of salt.…”

“…On Day 7, a second extinction test was conducted that was identical to the first extinction test, except that it was three hours in length. We chose the 1-week, post-stress time-point for the second extinction test because our previous work showed that chronic restraint stress caused an increase in palatable food seeking 7 days, but not one day, after the last restraint (Ball et al, 2017). See Fig.…”

“…Indeed, D 1 Rs play a critical role in several types of cocaine-seeking behaviors, including reinstatement triggered by acute stress, cocaine cues, and cocaine priming injections (Capriles et al, 2003; McFarland et al, 2004; McFarland and Kalivas, 2001; Park et al, 2002; Sun and Rebec, 2005). Moreover, we reported that the D 1 R antagonist, SCH-23390, when combined with chronic stress, attenuated the effects of stress on subsequent reinstatement of food seeking after extinction (Ball et al, 2015; Ball et al, 2016) and during forced abstinence (Ball et al, 2017). Thus, in the present study, we tested the hypothesis that SCH-23390 combined with repeated restraint stress would attenuate any effects of stress on subsequent cocaine-seeking behavior.…”