title: Acute antipsychotic treatments induce distinct c-Fos expression patterns in appetite-related neuronal structures of the rat brain.
abstract: A number of atypical antipsychotic drugs are known to perturb appetite regulation causing greater hyperphagia in humans and rodents than earlier generation typical agents. However, the neuronal structures that underlie hyperphagic effects are poorly understood. Arcuate nucleus (ArcN), paraventricular hypothalamic nucleus (PVN), paraventricular thalamic nucleus (PVA) and nucleus incertus (NI) have been implicated in appetite regulation. The NI is the principal source of the relaxin-3 (RLN3) peptide, which is reported to have orexigenic effects. Moreover, ArcN, PVN, and PVA receive RLN3 immunoreactive fibers from the NI and express relaxin family peptide type 3 (RXFP3) receptor. The present study was designed to evaluate the acute effects of clozapine (atypical), chlorpromazine (typical) and fluphenazine (typical) on c-Fos expression (a marker of neuronal response) in these appetite-related centers of the rat brain. The numbers of c-Fos expressing neurons in these structures were counted in immunofluorescence stained brain sections. Acute treatment with clozapine, chlorpromazine and fluphenazine differentially influenced c-Fos expression in these brain structures. This study is also the first demonstration that antipsychotics influence the NI. The patterns of the effects of these antipsychotics are related to their reported hyperphagic properties.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Ramamoorthy
authors.initials: R
authors.lastname: Rajkumar
authors.forename: Lionel Kee Yon
authors.initials: LK
authors.lastname: See
authors.forename: Gavin Stewart
authors.initials: GS
authors.lastname: Dawe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001066:Appetite / Q000187:drug effects* / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; C577472:RXFP3 protein, rat; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin