Opioidergic and dopaminergic modulation of cost/benefit decision-making in Long Evans Rats

Abstract

Highlights• We assess opioid and dopamine control of food intake with two cost/benefit decision-making tasks • Naloxone reduces operant responses for palatable food without affecting free chow intake • Haloperidol shifts behavior away from lever pressing and increases free chow feeding • Naloxone reduces preference for palatable banana pellets when no effort is involved • Dopamine antagonism reduces intake of both foods without altering preference AbstractEating disorders are associated with impaired decision-making and dysfunctional reward-related neurochemistry. The present study examined the potential contributions of dopamine and opioid signaling to these processes using two different decision-making tasks. In one task, Long Evans Rats chose between working for a preferred food (high-carbohydrate banana-flavored sucrose pellets) by lever pressing on a progressive-ratio schedule of reinforcement vs. obtaining less preferred laboratory chow that was concurrently available. In a second (effort-free) task, rats chose between the same two reinforcers when they were both available freely. Rats were trained in these tasks before receiving haloperidol (0.00, 0.05, 0.10 mg/kg, intraperitoneally (i.p.)) or naloxone (0.0, 1.5, 3.0 mg/kg, i.p.). In the first task, haloperidol decreased breakpoint, lever presses, number of reinforcers earned, and increased chow intake, whereas naloxone decreased breakpoint and number of reinforcers earned but had no effect on chow consumption. In the effort-free task, haloperidol reduced intakes of both foods without affecting preference, whereas naloxone selectively reduced the consumption of banana-pellets. The present findings support converging evidence suggesting that DA signaling affects processes more closely related to appetitive motivation, leaving other components of motivation unchanged. By contrast, opioid signaling appears to mediate aspects of hedonic feeding by selectively altering intakes of highly palatable foods. For preferred foods, both appetitive and consummatory aspects of food intake were altered by opioid receptor antagonism. Our findings argue against a general suppression of appetite by either compound, as appetite manipulations have been shown to unselectively alter intakes of both types of food regardless of the task employed.

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

“…Due to the substantial differences in g of EtOH, sucrose or saccharin contained per mL of these substances, intakes adjusted per body weight in Experiment 6 were expressed as mL/g, instead of g/kg. As described before (Morales et al, 2017), given that we used a within-subjects pharmacological design, the effects of NTX were analyzed using repeated measures Analysis of Variance (ANOVA). Apart from time (first 2 h vs. second 2 h), different simultaneously available concentrations or solutions were also considered repeated factors.…”

“…The endogenous opioid system has also been linked to sugar and other sweet rewards (Kelley et al, 2002;Olszewski and Levine, 2007;Berridge and Kringelbach, 2015). Intake of saccharin solutions increases by infusions of a mu opioid agonist into the ventral striatum (Zhang and Kelley, 2002), and pharmacological antagonism of opioid receptors can reduce consumption of sucrose and saccharin (Biggs and Myers, 1998;June et al, 2004;Morales et al, 2017). Also, excessive sugar intake can produce withdrawal-like symptoms associated with alterations in opioid receptor signaling (Colantuoni et al, 2002;Avena et al, 2009).…”

“…Opioid receptors, and in particular the mu receptor can also influence the motivational and psychomotor stimulant effects of EtOH and other reinforcers (Gianoulakis, 2001;Pastor et al, 2005Pastor et al, , 2011Pastor and Aragon, 2006;Kamdar et al, 2007). Pharmacological activation of mu-opioid receptors can enhance saccharin or EtOH intakes (Zhang and Kelley, 2002), while inactivation can reduce consumption of sucrose, saccharin or EtOH (June et al, 2004;Kamdar et al, 2007;Tarragón et al, 2012;Avena et al, 2014;Morales et al, 2017). The opioid receptor antagonist naltrexone (NTX), a compound with high affinity for mu-opioid receptors, is used to treat alcoholism (Volpicelli et al, 1992;Kiefer et al, 2003;Jonas et al, 2014), and in combination with bupropion (marketed as Contrave™) has recently been approved for the treatment of binge-eating disorder and weight-loss management.…”