Eating high fat chow selectively impacts sensitivity to drugs acting on dopamine D3/D2 but not serotonin 2A receptors

Abstract

Feeding conditions (e.g., type and quantity of food) can impact sensitivity to drugs acting on monoamine systems including direct‐and indirect‐acting dopamine (DA) receptor agonists; much less is known about the impact of different feeding conditions on drugs acting on serotonin (5‐HT) systems. Male Sprague‐Dawley rats had free access to high fat chow (34.3% fat; n = 8) or standard chow (5.7% fat; n = 7). Rats eating high fat chow gained more weight than rats eating standard chow and they became insulin resistant within 2 weeks. Moreover, rats eating high fat chow were more sensitive to yawning induced by quinpirole (DA receptor agonist; 0.0032–0.32 mg/kg) as compared with rats eating standard chow. Throughout the study, head twitching and changes to body temperature produced by the 5‐HT2A receptor agonist DOM (1‐(2, 5‐dimethoxy‐4‐methylphenyl)‐2‐aminopropane; 0.1–3.2 mg/kg) were not significantly different between groups. These results indicate that diet differentially impacts drugs acting on DA and 5‐ HT systems. Eating high fat chow selectively sensitized rats to the behavioral effects of a DA agonist, suggesting that eating high fat food might increase sensitivity to, and therefore vulnerability to abuse, drugs acting on dopamine systems (e.g., cocaine). CPF is supported by the NIDA Senior Scientist Award (K05 DA017918).