PRECLINICAL STUDY: Ghrelin stimulates locomotor activity and accumbal dopamine‐overflow via central cholinergic systems in mice: implications for its involvement in brain reward
Tóm tắt
It is becoming increasingly apparent that there is a degree of neurochemical overlap between the reward systems and those regulating energy balance. We therefore investigated whether ghrelin, a stomach‐derived and centrally derived orexigenic peptide, might act on the reward systems. Central ghrelin administration (1 µg/µL, to the third ventricle) induced an acute increase in locomotor activity as well as dopamine‐overflow in the nucleus accumbens, suggesting that ghrelin can activate the mesoaccumbal dopamine system originating in the ventral tegmental area, a system associated with reward and motivated behaviour. The cholinergic afferents to the ventral tegmental area have been implicated in natural reward and in regulating mesoaccumbal dopamine neurons. The possibility that nicotinic receptors are involved in mediating the stimulatory and dopamine‐enhancing effects of ghrelin is supported by the findings that peripheral injection of the unselective nicotinic antagonist mecamylamine (2.0 mg/kg) blocked these ghrelin‐induced effects. Tentatively, ghrelin may, via activation of the acetylcholine–dopamine reward link, increase the incentive values of signals associated with motivated behaviours of importance for survival such as feeding behaviour. It will be important to discover whether this has therapeutic implications for compulsive addictive behaviours, such as eating behaviour disorders and drug dependence.
Từ khóa
Tài liệu tham khảo
Butcher LL, 2003, The Rat Nervous System, 1257
Engel JA, 1977, Recent Advances in the Study of Alcoholism (Excerpta Medica International Congress Series 407), 16
Engel JA, 1977, Cathecolamines and Behavior, 1
Esch T, 2004, The neurobiology of pleasure, reward processes, addiction and their health implications, Neuroendocrinol Lett, 25, 235
Franklin KBJ, 1996, The Mouse Brain in Stereotaxic Coordinates
LarssonA(2004)On cholinergic mechanisms involved in ethanol reinforcement—a behavioural and neurochemical study in rodents.Thesis.ISBN: 91‐628‐6202‐2. öIntellecta Docusys Göteborg Sweden.