Background
The hypothalamic neuropeptide melanin-concentrating hormone (MCH) plays a critical
role in energy homeostasis. Abundant expression of the MCH receptor is observed outside
the hypothalamus, especially in the dorsal and the ventral striatum, raising the possibility
that MCH modulates the function of the midbrain dopamine neurons and associated circuitry.
Methods
The MCH receptor 1 (MCHR1) expression was assessed by in situ hybridization. Expression
of dopamine transporter (DAT) and the dopamine D1 and D2 receptor (D1R and D2R) subtypes
in the caudate-putamen (CPu) and the nucleus accumbens (Acb) was evaluated by immunoblotting.
Amperometry in ex vivo slices of the Acb was used to measure evoked-dopamine release
in MCH−/ − mice. Catalepsy in MCH+/+ and MCH−/− mice was assessed by the bar test after haloperidol injection. Locomotor activity
was measured after acute and chronic treatment with amphetamine and after dopamine
reuptake inhibitor GBR 12909 administration.
Results
The psychostimulant amphetamine caused enhanced behavioral sensitization in MCH−/− mice. We found significantly elevated expression of the DAT in the Acb of MCH−/− mice. The DAT-mediated uptake of dopamine was also enhanced in MCH−/− mice consistent with increased expression of DAT. We also found that evoked dopamine
release is significantly increased in the Acb shell of MCH−/− mice. The GBR 12909 administration increased the locomotor activity of MCH−/− mice significantly above that of MCH+/+ mice.
Conclusions
These results demonstrate that MCH, in addition to its known role in feeding and weight
regulation, plays a critical role in regulating Acb dopamine signaling and related
behavioral responses.
Key Words
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Article info
Publication history
Published online: February 18, 2008
Accepted:
December 17,
2007
Received in revised form:
December 17,
2007
Received:
July 20,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
