Submitted on May 17, 2005
Accepted on October 3, 2005
Effects of central and systemic administration of leptin on neurotransmitter concentrations in specific areas of the hypothalamus
Kimberly A Clark1, Sheba M. J MohanKumar2, Badrinarayanan S Kasturi3, and P. S MohanKumar2*
1 Neuroscience Program, Michigan State University, East Lansing, MI, USA
2 Neuroscience Program, Michigan State University, East Lansing, MI, USA; Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USA
3 Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, USA
* To whom correspondence should be addressed. E-mail: mohankumar{at}cvm.msu.edu.
Leptin, a hormone produced by adipocytes has been shown to affect a number of central functions such as regulation of the hypothalamo-pituitary-adrenal axis, feeding, and body weight regulation. Since hypothalamic monoamines are intricately involved in the regulation of these functions, we hypothesized that leptin may produce its effects by altering the activity of these neurotransmitters. To test this, male rats received peripheral (i.p.; 0, 100 or 500 µg), or central (i.c.v.; 0 or 5 µg) injections of leptin. The animals were sacrificed 5 h later and their brains were removed, frozen and sectioned. Serum was collected to measure leptin and corticosterone by RIA. The paraventricular nucleus (PVN), arcuate nucleus (AN), ventromedial hypothalamus (VMH), dorsomedial dorsal nucleus (DMD), median eminence (ME) and medial preoptic area (MPA) were obtained using Palkovits' microdissection technique and monoamine concentrations in these areas were determined using HPLC-EC. Intraperitoneal administration of leptin increased serum leptin concentrations in a dose-dependent manner (p<0.05). Both i.p. and i.c.v.
administration of leptin decreased serum corticosterone significantly (p<0.05). Norepinephrine (NE) concentration decreased significantly in the PVN, AN, and VMH after both i.p. and i.c.v. administration of leptin (p<0.05). NE concentrations decreased significantly in the DMD after
i.c.v. administration of leptin (p<0.05). Leptin treatment (both i.p. and i.c.v.) decreased dopamine (DA) concentrations significantly in the PVN. Serotonin (5-HT) concentration decreased significantly in the PVN after both i.p. and i.c.v. injections of leptin and decreased in
the VMH only with i.c.v. treatment of leptin. Leptin did not affect any of the monoamines in the ME and MPA. These results indicate that both central and systemic administration of leptin can affect hypothalamic monoamines in a region specific manner, which in turn could mediate many of leptin's central and neuroendocrine effects.
