title: Evidence of increased dopamine receptor signaling in food-restricted rats.
abstract: 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.
authors.affiliation: Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. kc16@nyu.edu
authors.forename: K D
authors.initials: KD
authors.lastname: Carr
authors.forename: Y
authors.initials: Y
authors.lastname: Tsimberg
authors.forename: Y
authors.initials: Y
authors.lastname: Berman
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005508:Food Deprivation / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D016760:Proto-Oncogene Proteins c-fos; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine