Cocaine-induced plasticity, motivation, and cue responsivity do not differ in obesity-prone vs obesity-resistant rats; implications for food addiction

RATIONALE: Compared to obesity-resistant rats, obesity-prone rats consume more food, work harder to obtain food, show greater motivational responses to food-cues, and show greater striatal plasticity in response to eating sugary/fatty foods. Therefore, it is possible that obesity-prone rats may also be more sensitive to the motivational properties of cocaine and cocaine-paired cues, and to plasticity induced by cocaine. OBJECTIVE: To examine baseline differences in motivation for cocaine and effects of intermittent access (IntA) cocaine self-administration on cocaine motivation, neurobehavioral responsivity to cocaine-paired cues, and locomotor sensitization in male obesity-prone vs obesity-resistant rats. METHODS: Intravenous cocaine self-administration was used to examine drug-taking and drug-seeking in males. Motivation for cocaine was measured using a within session threshold procedure. Cue-induced c-Fos expression in mesocorticolimbic regions was measured. RESULTS: Drug-taking and drug-seeking, cue-induced c-Fos, locomotor sensitization, and preferred level of cocaine consumption (Q(0)) were similar between obesity-prone and obesity-resistant groups. Maximal responding during demand testing (R(max)) was lower in obesity-prone rats. IntA experience enhanced motivation for cocaine (P(max)) in obesity-prone rats. CONCLUSIONS: The results do not support robust inherent differences in motivation for cocaine, cue-induced cocaine seeking, or neurobehavioral plasticity induced by IntA in obesity-prone vs obesity-resistant rats. This contrasts with previously established differences seen for food and food cues in these populations and shows that inherent enhancements in motivation for food and food-paired cues do not necessarily transfer to drugs and drug-paired cues. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-023-06327-5.