Background: Food is a natural reward able to stimulate rewarding brain circuits by the activation of at least three senses: taste, smell and sight. From the periphery the pleasant experience reaches the Central Nervous System (CNS) stimulating the neurotransmitter activity in several brain systems that are involved in the complex regulation of food intake and energy homeostasis. The dopaminergic (DAergic) mesolimbic system is one of the most important reward brain circuits and a robust literature demonstrates an involvement of mesolimbic and mesocortical dopamine (DA) transmission in food consumption. Furthermore, other neuronal systems, such as the orexinergic one, are involved in the modulation of the rewarding properties of food and most of them seem to converge on mesolimbic dopaminergic system. Given these premises the aim of our study was to investigate the effect of OxA on the basal and feedingactivated DA transmission in the NAc shell. Methods: OxA is a large peptide and does not cross the blood–brain barrier. For this reason it was loaded on two kinds of liposomes: antitransferrin- monoclonal antibodies (OX26-mAb) and lactoferrin-modified stealth liposomes. The effect of IV administration of both OxA liposomes on NAc shell DA was studied by microdialysis in freely moving rats. Results: We found that OxA increased basal shell DA transmission as well as potentiated its responsiveness to palatable food (sucrose pellets) and increased feeding. The effect of OxA on DA and feeding was prevented by Ox receptor1 antagonist. Conclusions: These results demonstrate for the first time in vivo the facilitatory effect of OxA on DA transmission. We hypothesize that during feeding, hypothalamic orexinergic neurons release OxA in the VTA; OxA interacts with OxR1 located on VTA dopaminergic neurons promoting DA release in the terminal areas, such as the NAc shell. Further studies need to be performed in order to evaluate the involvement of OxA and DA in food addiction.
Responsiveness of mesolimbic and mesocortical dopamine transmission during food and drugs of abuse consumption
Valentina Bassareo
;Flavia Cucca;Roberto Frau;Francesco Corrias;Michele Schlich;Pierluigi Caboni;Anna Maria Fadda;
2019-01-01
Abstract
Background: Food is a natural reward able to stimulate rewarding brain circuits by the activation of at least three senses: taste, smell and sight. From the periphery the pleasant experience reaches the Central Nervous System (CNS) stimulating the neurotransmitter activity in several brain systems that are involved in the complex regulation of food intake and energy homeostasis. The dopaminergic (DAergic) mesolimbic system is one of the most important reward brain circuits and a robust literature demonstrates an involvement of mesolimbic and mesocortical dopamine (DA) transmission in food consumption. Furthermore, other neuronal systems, such as the orexinergic one, are involved in the modulation of the rewarding properties of food and most of them seem to converge on mesolimbic dopaminergic system. Given these premises the aim of our study was to investigate the effect of OxA on the basal and feedingactivated DA transmission in the NAc shell. Methods: OxA is a large peptide and does not cross the blood–brain barrier. For this reason it was loaded on two kinds of liposomes: antitransferrin- monoclonal antibodies (OX26-mAb) and lactoferrin-modified stealth liposomes. The effect of IV administration of both OxA liposomes on NAc shell DA was studied by microdialysis in freely moving rats. Results: We found that OxA increased basal shell DA transmission as well as potentiated its responsiveness to palatable food (sucrose pellets) and increased feeding. The effect of OxA on DA and feeding was prevented by Ox receptor1 antagonist. Conclusions: These results demonstrate for the first time in vivo the facilitatory effect of OxA on DA transmission. We hypothesize that during feeding, hypothalamic orexinergic neurons release OxA in the VTA; OxA interacts with OxR1 located on VTA dopaminergic neurons promoting DA release in the terminal areas, such as the NAc shell. Further studies need to be performed in order to evaluate the involvement of OxA and DA in food addiction.
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