title: Long-term, calorie-restricted intake of a high-fat diet in rats reduces impulse control and ventral striatal D2 receptor signalling - two markers of addiction vulnerability.
abstract: High impulsivity, mediated through ventral striatal dopamine signalling, represents an established risk factor for substance abuse, and may likewise confer vulnerability to pathological overeating. Mechanistically, the assumption is that trait impulsivity facilitates the initiation of maladaptive eating styles or choices. However, whether consumption of appetitive macronutrients themselves causes deficits in impulse control and striatal signalling, thereby contributing to cognitive changes permissive of overeating behaviour, has yet to be considered. We examined the effects of chronic maintenance on restricted equicaloric, but high-fat or high-sugar, diets (48 kcal/day; 60 kcal% fat or sucrose) on rats' performance in the five-choice serial reaction time task, indexing impulsivity and attention. Markers of dopamine signalling in the dorsal and ventral striatum, and plasma insulin and leptin levels, were also assessed. Rats maintained on the high-fat diet (HFD) were more impulsive, whereas the high-sugar diet (HSD) did not alter task performance. Importantly, body weight and hormone levels were similar between groups when behavioural changes were observed. Maintenance on HFD, but not on HSD, reduced the levels of dopamine D2 receptor (D2 R), cAMP response element-binding protein (CREB) and phosphophorylated CREB (Ser133) proteins in the ventral, but not dorsal, striatum. D2 R expression in the ventral striatum also negatively correlated with impulsive responding, independently of diet. These data indicate that chronic exposure to even limited amounts of high-fat foods may weaken impulse control and alter neural signalling in a manner associated with vulnerability to addictions - findings that have serious implications for the propagation of uncontrolled eating behaviour in obesity and binge-eating disorder.
authors.affiliation: Department of Psychology, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, British Columbia, Canada.|UBC Institute of Mental Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Adams
authors.affiliation: Department of Psychology, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, British Columbia, Canada.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Sussman
authors.affiliation: Department of Psychology, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, British Columbia, Canada.
authors.forename: Sukhbir
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anna M
authors.initials: AM
authors.lastname: D'souza
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
authors.affiliation: Department of Psychology, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, British Columbia, Canada.|UBC Institute of Mental Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Winstanley
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology; D001774:Blood Chemical Analysis; D001835:Body Weight; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004038:Diet, Reducing / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D056344:Executive Function / Q000502:physiology; D015151:Immunoblotting; D007175:Impulsive Behavior / Q000502:physiology*; D007266:Inhibition, Psychological; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000502:physiology; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013997:Time Factors; D066328:Ventral Striatum / Q000503:physiopathology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C000607792:DRD2 protein, rat; D019422:Dietary Sucrose; D007328:Insulin; D020738:Leptin; D017448:Receptors, Dopamine D2
keywords: CREB; dopamine; five-choice serial reaction time task; impulsivity; nucleus accumbens