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Caloric restriction and increased dopamine receptor signaling.



 
 
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Old March 15th, 2004, 09:41 PM
Tim
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Default Caloric restriction and increased dopamine receptor signaling.

1: Neuroscience. 2003;119(4):1157-67. Related Articles, Links


Evidence of increased dopamine receptor signaling in food-restricted
rats.

Carr KD, Tsimberg Y, Berman Y, Yamamoto N.

Department of Psychiatry, Millhauser Laboratories, New York University
School of Medicine, 550 First Avenue, New York, NY 10016, USA.


It is well established that chronic food restriction enhances
sensitivity to the rewarding and motor-activating effects of abused
drugs. However, neuroadaptations underlying these behavioral effects
have not been characterized. The purpose of the present study was to
explore the possibility that food restriction produces increased
dopamine (DA) receptor function that is evident in behavior, signal
transduction, and immediate early gene expression. In the first two
experiments, rats received intracerebroventricular (i.c.v.) injections
of the D1 DA receptor agonist SKF-82958, and the D2/3 DA receptor
agonist quinpirole. Both agonists produced greater motor-activating
effects in food-restricted than ad libitum-fed rats. In addition,
Fos-immunostaining induced by SKF-82958 in caudate-putamen (CPu) and
nucleus accumbens (Nac) was greater in food-restricted than ad
libitum-fed rats, as was staining induced by quinpirole in globus
pallidus and ventral pallidum. In the next two experiments, neuronal
membranes prepared from CPu and Nac were exposed to SKF-82958 and
quinpirole. Despite the documented involvement of cyclic AMP (cAMP)
signaling in D1 DA receptor-mediated c-fos induction, stimulation of
adenylyl cyclase (AC) activity by SKF-82958 in CPu and Nac did not
differ between groups. Food restriction did, however, decrease AC
stimulation by the direct enzyme stimulant, forskolin, but not NaF or
MnCl(2), suggesting a shift in AC expression to a less catalytically
efficient isoform. Finally, food restriction increased
quinpirole-stimulated [(35)S]guanosine triphosphate-gammaS binding in
CPu, suggesting that increased functional coupling between D2 DA
receptors and G(i) may account for the augmented behavioral and
pallidal c-Fos responses to quinpirole. Results of this study support
the hypothesis that food restriction leads to neuroadaptations at the
level of postsynaptic D1 and D2 receptor-bearing cells which, in turn,
mediate augmented behavioral and transcriptional responses to DA. The
signaling pathways mediating these augmented responses remain to be
fully elucidated.

PMID: 12831870 [PubMed - indexed for MEDLINE]
 




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