Leptin promotes dopamine transporter and tyrosine hydroxylase activity in the nucleus accumbens of Sprague-Dawley rats.
Adipocytes produce the hormone, leptin, in proportion to fat mass to signal the status of body energy stores to the central nervous system, thereby modulating food intake and energy homeostasis. In addition to controlling satiety, leptin suppresses the reward value of food, which is controlled by the mesolimbic dopamine (DA) system. Previous results from leptin-deficient ob/ob animals suggest that chronic leptin deficiency decreases DA content in the mesolimbic DA system, thereby decreasing the response to amphetamine (AMPH). The extent to which these alterations in the mesolimbic DA system of ob/ob animals may mirror the leptin response of normal animals has remained unclear, however. We therefore examined the potential short-term modulation of the mesolimbic DA system by leptin in normal animals. We show that 4 h of systemic leptin treatment enhances AMPH-stimulated DA efflux in the nucleus accumbens (NAc) of Sprague-Dawley rats. While acute leptin treatment increased NAc tyrosine hydroxylase activity, total tyrosine hydroxylase and DA content were unchanged at this early time point. Leptin also increased NAc DA transporter activity in the absence of changes in cell surface or total DA transporter. Thus, leptin modulates the mesolimbic DA system via multiple acute mechanisms, and increases AMPH-mediated DA efflux in normal animals.
Perry
Maura L
ML
Chemistry Department, University of Michigan, Ann Arbor, MI 48109, USA.
Leinninger
Gina M
GM
Chen
Rong
R
Luderman
Kathryn D
KD
Yang
Hongyan
H
Gnegy
Margaret E
ME
Myers
Martin G
MG
Kennedy
Robert T
RT
D000661:Amphetamine / Q000819:agonists; D000818:Animals; D001066:Appetite / Q000502:physiology; D001069:Appetite Regulation / Q000502:physiology; D004298:Dopamine / Q000096:biosynthesis*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000819:agonists; D020738:Leptin / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D020738:Leptin; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
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