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Chronic food restriction alters purinergic receptor mRNA expression in the nucleus accumbens of the rat
Author(s) -
Krügel Ute,
Seidel Bertholt,
Spies Oliver,
Kittner Holger,
Illes Peter,
Kiess Wieland
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10207
Subject(s) - nucleus accumbens , endocrinology , medicine , purinergic receptor , p2 receptor , receptor , adenosine , leptin , biology , cart , chemistry , dopamine , mechanical engineering , engineering , obesity
ATP and its metabolite adenosine activate membrane receptors thought to be functionally relevant in the mediation of reward and reinforcement (e.g., feeding behavior). In this study, the effects of restricted feeding on the purinergic transmission at the level of the adenosine A 2A and ADP/ATP‐sensitive P2Y 1 receptor mRNA were investigated in the rat nucleus accumbens after 3 days of acute food deprivation and after 10 days when adaptive changes can be expected to occur. Furthermore, plasma leptin and the expression of its receptor mRNA (long form) to characterize the status of satiety were examined as well as the expression of the cocaine‐ and amphetamine‐related transcript (CART) mRNA as a possible marker for changes in the sensitiveness of the reward system. Plasma levels of the anorectic peptide leptin were reduced within 3 days of feeding restriction; the mRNA of the leptin receptor was elevated at day 10. The P2Y 1 receptor mRNA expression showed the same time course, whereas the A 2A receptor mRNA reached the control level on day 10 after a downregulation found on day 3. CART mRNA expression was decreased in the acute situation and upregulated after 10 days. The data indicate that the accumbal gene expression during food restriction is triggered by peripheral signals like plasma leptin concentration and by neuronal signals in the CNS, including extracellular adenosine and ADP/ATP, and that the investigated receptor mRNAs are regulated to habituate to the reduced nutrition. In conclusion, chronic food restriction increases the mesolimbic sensitivity directed to achieve satisfaction and reward via regulation of mRNA expression involving that of P2Y 1 and A 2A receptors in a functionally antagonistic manner. Drug Dev. Res. 59:95–103, 2003. © 2003 Wiley‐Liss, Inc.