Food 'four' thought : examining sigma-1 receptor antagonist PD144418 on food reinforced behaviors

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] A large number of individuals consume a poor diet, including food and beverages that are high in fat, salts, and/or sugar, often in conjunction with a lack of exercise. Alterations in one's feeding behaviors have implications as it relates to the prevention and treatment of one's risk of obesity and of common health consequences associated with being overweight or obese. Therefore, exploring a potential pharmacological manipulation of feeding behaviors could provide a treatment option for those who have disordered eating patterns. The potent and selective sigma-1 receptor antagonist PD144418 was examined as a potential therapeutic target regarding motivational aspects of food-reinforced operant behaviors. Additionally, experiments looked at whether biological factors (i.e., sex) and physiological factors (i.e., energy intake and physical activity) moderate the effects. Results indicated PD144418 decreases an animal's motivational effort, or work, for food pellets but has no impact on the consumption of freely available food pellets. Such effects on motivational effort to work for food occur regardless of sex. However, alterations in physiological factors, such as energy intake, appear to be sex dependent as PD144418 selectively reduces female motivation for food during negative energy balance. Moreover, in males, PD144418, in conjunction with access to voluntary physical activity, does not alter food-reinforced operant responding. How PD144418 may be exerting its effects on motivational aspects of feeding is via alterations in dopaminergic signaling, as coadministration of PD144418 along with an intra-accumbens infusion of d-amphetamine, a dopamine agonist, but not DAMGO, a mu-opioid agonist attenuates operant responding.