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

• 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 microg/microL, 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Afferent Pathways

drug effects

physiopathology

Animals

Brain

physiopathology

Cholinergic Fibers

drug effects

physiology

Dopamine

metabolism

Eating Disorders

physiopathology

Injections

Intraventricular

Male

Mecamylamine

pharmacology

Mice

Mice

Inbred Strains

Motor Activity

drug effects

physiology

Nucleus Accumbens

drug effects

physiopathology

Peptide Hormones

pharmacology

Receptors

Nicotinic

drug effects

physiology

Reward

Substance-Related Disorders

physiopathology

Tegmentum Mesencephali

drug effects

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)