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Palatability driven feeding and voluntary physical activity are mediated by and influence similar neural mechanisms, notably through the actions of opioids within the nucleus accumbens. Recent studies suggest that access to a voluntary running wheel results in sex dependent behavioral and physiological adaptations related to opioid mediated palatability-driven feeding. To explore this relationship, male and female Wistar rats were given either access to a voluntary running wheel (RUN group) or no access (SED group) for one week prior to being stereotaxically implanted with bilateral cannulae targeting the nucleus accumbens. Following 7 days of recovery, with RUN or SED conditions continuing the duration of the experiment, all rats were assessed daily (2 h/day) for feeding behavior of concurrently accessible high-carbohydrate and high-fat diet for one week. Following this week, all rats were administered the μ-opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) (0.0025 μg, 0.025 μg, or 0.25 μg/0.5 μl/side) or the opioid antagonist naloxone (20 μg/0.5 μl/side) into the nucleus accumbens and given concurrent access (2 h) to both diets. All groups expressed a significant baseline preference for the high-carbohydrate diet. DAMGO administration, compared to saline treatment, led to significant increased consumption of the high-carbohydrate diet in all treatment groups. While high-fat diet consumption also increased following DAMGO administration, the influence of DAMGO was much more robust for the preferred high-carbohydrate diet in all groups. Compared to males, females consumed significantly more of both diets at baseline and following DAMGO treatment. Both male and female rats in the RUN condition consumed more high-carbohydrate diet compared to rats in the SED condition. While males exhibited similar increased consumption of both diets regardless of RUN or SED condition, females in the RUN condition displayed a greater sensitivity to DAMGO-driven consumption of the preferred high-carbohydrate, compared to SED females.

Sigma-1 (σ1) receptors have been investigated for their involvement in learning, rewarding and motivational processes, particularly as it relates to substances of abuse. Few studies have examined the effects of σ1 receptor agonists and antagonists on the rewarding and motivational properties of natural reinforcers, such as food. Studies that have investigated σ1 receptor agonists and antagonists has produced conflicting results. σ1 receptor antagonist PD144418 has been found to produce a dose-dependent attenuation of locomotor activity induced by cocaine, and by itself, does not suppress basal locomotor activity in mice. However, its effects on reward and motivation as it relates to food are unknown. The present study examined the involvement of σ 1 receptors in mediating the rewarding and motivational properties of food using an operant task. The results indicated that at the highest dose (10 μmol/kg), PD144418 significantly attenuated the number of active lever responses for chow pellets but did not decrease the number of active lever responses for sucrose pellets under a fixed ratio (FR2) schedule of reinforcement. However, under a progressive ratio (PR) reinforcement schedule, 10 μmol/kg of PD14418 significantly reduced the breakpoint, a measure indicative of effort or motivation, for both chow and sucrose pellets. When ad libitum chow or sucrose pellets were made freely available (i.e. no lever press required) inside the operant chamber, 10 μmol/kg, PD144418 did not have an effect on number of pellets consumed. These findings indicate that PD144418 reduces the motivational effort of a food reinforced behavior.

Feeding behaviors can be modified via homeostatic and hedonic mechanisms. Homeostasis, while primarily concerned with maintaining energy balance via food consumption and energy expenditure, can alter food reward and motivation in response to food deprivation. Alternatively, reward and motivation of food is also driven by its palatability or hedonic nature, and this process can be augmented by opioid receptor activation. The present study examined sex differences in the motivational properties of sucrose pellets through manipulation of homeostatic and hedonic processes via acute food deprivation and acute systemic administration of morphine, respectively. The results showed that regardless of sex, systemic injections of morphine did not alter the motivation to obtain a sucrose pellet on a progressive ratio schedule of reinforcement but does significantly increase consumption of sucrose pellets when freely available. Male and female rats demonstrated similar increased consumption of sucrose pellets under free feeding conditions following acute (24-hours) food deprivation, compared to the non-deprived conditions. Overall, the findings from these experiments indicate that female rats work harder in order to obtain a sucrose pellet (under a Progressive Ratio (PR) schedule of reinforcement) and consume more sucrose pellets than males. However, while acute morphine administration causes similar increases on feeding in males and females, it does not alter motivation as measured by breakpoint on a PR schedule of reinforcement.