Operant behavior to obtain palatable food modifies neuronal plasticity in the brain reward circuit

Abstract

Palatability enhances food intake by hedonic mechanisms that prevail over caloric necessities. Different studies have demonstrated the role of endogenous cannabinoids in the mesocorticolimbic system in controlling food hedonic value and consumption. We hypothesize that the endogenous cannabinoid system could also be involved in the development of food-induced behavioral alterations, such as food-seeking and binge-eating, by a mechanism that requires neuroplastic changes in the brain reward pathway. For this purpose, we evaluated the role of the CB1 cannabinoid receptor (CB1-R) in the behavioral and neuroplastic changes induced by operant training for standard, highly caloric or highly palatable isocaloric food using different genetics, viral and pharmacological approaches. Neuroplasticity was evaluated by measuring changes in dendritic spine density in neurons previously labeled with the dye DiI. Only operant training to obtain highly palatable isocaloric food induced neuroplastic changes in neurons of the nucleus accumbens shell and prefrontal cortex that were associated to changes in food-seeking behavior. These behavioral and neuroplastic modifications induced by highly palatable isocaloric food were dependent on the activity of the CB1-R. Neuroplastic changes induced by highly palatable isocaloric food are similar to those produced by some drugs of abuse and may be crucial in the alteration of food-seeking behavior leading to overweight and obesity.

Effects of CB1 cannabinoid receptor activation in the nucleos accumbens shell on feeding behavior.

“…Furthermore, behavioral experiments have shown that rimonabant bilaterally microinjected into the NAcS selectively decreased highly palatable food intake in an operant task (Guegan, et al, 2013). Our results confirm and extend the previous evidence that intra-accumbens administration of anandamide or 2-AG increase standard chow consumption (Soria-Gómez, et al, 2007;Kirkham, et al, 2002) by a behavioral-specific mechanism.…”

“…Nevertheless, in the present study both cannabinoid agonists were administered intra-NAcS and the behavioral profile elicited should not be considered as a general stimulating effect, since the endogenous cannabinoid system is strongly involved in the development of food-induced behavioral alterations, such as foodseeking. Supporting this notion, it was demonstrated that the deletion of CB1R decreased operant behavior and the motivation to obtain highly palatable food in CB1 KO mice (Guegan, et al, 2013). Furthermore, the findings that CB1R KO rodents are resistant to diet-induced obesity (Ravinet-Trillou, Delgorge, Menet, Arnone & Soubrié, 2004), and that over-activity of the endocannabinoid system promotes an obese phenotype (Maccarrone, et al, 2010), in conjunction with the cannabinoid-induced increase of activity observed in this study, suggest a functional connection between the endocannabinoid system, ineffective inhibition of responses and obesity.…”

Differential expression of CART in feeding and reward circuits in binge eating rat model

“…As in the case of drug addiction, BE seems to evoke neuroplastic changes in hypothalamic and extra-hypothalamic regions [62,63]. We observed increased percent area of CART and synaptophysin co-expressing contents in the LH of BE rats as compared to that in the non-binge naïve animals.…”

Epigenética, Cuidados Maternais e Vulnerabilidade ao Estresse: Conceitos Básicos e Aplicabilidade

“…Um exemplo da alteração ocorrida na circuitaria cerebral do sistema de recompensa após condicionamento operante da resposta obtenção de comida foi apresentado na pesquisa de Guegan et al (2013). O estudo mostrou alterações na densidade dos dendritos dos neurônios no nucleus accumbens após condicionamento operante de ingestão de alimentos de alto valor calórico.…”