Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice.
Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed. Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self-administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA. We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood.
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
M Carmen
MC
Blanco-Gandía
Neurobiology of Behavior Research Group (GReNeC), Department of Health and Experimental Sciences, University Pompeu Fabra, IMIM (Hospital del Mar), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
Lídia
L
Cantacorps
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
Auxiliadora
A
Aracil-Fernández
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
Sandra
S
Montagud-Romero
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
María A
MA
Aguilar
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
Jorge
J
Manzanares
Neurobiology of Behavior Research Group (GReNeC), Department of Health and Experimental Sciences, University Pompeu Fabra, IMIM (Hospital del Mar), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
Olga
O
Valverde
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain.
José
J
Miñarro
Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia, Spain. Electronic address: marta.rodriguez@uv.es.
Marta
M
Rodríguez-Arias
D000818:Animals; D001007:Anxiety / Q000209:etiology; D001835:Body Weight; D002032:Bulimia / Q000150:complications / Q000378:metabolism* / Q000523:psychology*; D003042:Cocaine / Q000008:administration & dosage*; D003214:Conditioning, Classical / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D058999:Drug-Seeking Behavior; D015870:Gene Expression; D054439:Ghrelin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000378:metabolism
D054439:Ghrelin; D020738:Leptin; D043884:Receptor, Cannabinoid, CB1; D017450:Receptors, Opioid, mu; D003042:Cocaine; D003345:Corticosterone
Binge eating; Cocaine; Conditioned place preference; Fat; Gene expression; Self-administration