Sigma-1 receptor antagonist, PD144418, selectively reduces female motivation for food during negative energy balance

Sigma-1 (σ₁) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ₁ receptor antagonist, 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. Moreover, PD144418 decreases the motivational effort of a food-reinforced behavior in male rats, without altering appetite or food palatability. It remains unknown whether the PD144418 can alter the motivational effort of a food-reinforced behavior in response to altered energy homeostasis, as is the case under 24 -h food deprivation. Additionally, while the previous experiments indicate effects in male rats, there has been no research examining the effects of PD144418, or any other σ₁ receptor antagonist, on motivational aspects of feeding in females. The present study examined the effects of PD144418 on motivational aspects of feeding in male and female rats using an operant task under sated or food deprived conditions. Results indicated that when animals are sated, at the highest dose (10 μmol/kg), under a progressive ratio (PR) reinforcement schedule, PD144418 significantly attenuated the breakpoint and the number of active lever responses for sucrose pellets in both males and females. When animals are in a state of energy deficit, as is the case following 24-hr food deprivation, PD144418 does not alter motivationally driven operant responding as measured by the breakpoint in either sex but does alter the number of earned reinforcers responses in females.