PRECLINICAL STUDY: Ghrelin stimulates locomotor activity and accumbal dopamine‐overflow via central cholinergic systems in mice: implications for its involvement in brain reward

Addiction Biology - Tập 11 Số 1 - Trang 45-54 - 2006
Elisabet Jerlhag1, Emil Egecioglu2, Suzanne L. Dickson2, Malin Andersson1, Lennart Svensson1, Jörgen A. Engel1
1Institute of Pharmacology and Physiology, Department of Pharmacology, Göteborg University, Sweden and
2Institute of Pharmacology and Physiology, Division of Endocrinology, Göteborg University, Sweden

Tóm tắt

ABSTRACTIt 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.

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Addiction Biology

Tập 11 Số 1

45-54

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