title: Involvement of CART in estradiol-induced anorexia.
abstract: Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response.
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, Maharashtra, 440 033, India.
authors.forename: Manoj P
authors.initials: MP
authors.lastname: Dandekar
authors.forename: Kartik T
authors.initials: KT
authors.lastname: Nakhate
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
authors.forename: Nishikant K
authors.initials: NK
authors.lastname: Subhedar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D000906:Antibodies / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000009:adverse effects*; D004965:Estrogen Antagonists / Q000008:administration & dosage; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D000906:Antibodies; D004965:Estrogen Antagonists; D004967:Estrogens; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D013629:Tamoxifen; D004958:Estradiol