title: Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y.
abstract: OBJECTIVE
  Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY).
  
  
  METHODS
  Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α₂-adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y₁ receptor agonist, [Leu³¹, Pro³⁴]-NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post-injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry.
  
  
  RESULTS
  Agmatine robustly increased feeding in a dose-dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu³¹, Pro³⁴]-NPY potentiated the agmatine-induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments.
  
  
  CONCLUSIONS
  The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α₂-adrenoceptors within the PVN. This signifies the importance of agmatine or α₂-adrenoceptor modulators in the development of novel therapeutic agents to treat feeding-related disorders.
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra, India.
authors.forename: B G
authors.initials: BG
authors.lastname: Taksande
authors.forename: N R
authors.initials: NR
authors.lastname: Kotagale
authors.forename: K T
authors.initials: KT
authors.lastname: Nakhate
authors.forename: P D
authors.initials: PD
authors.lastname: Mali
authors.forename: D M
authors.initials: DM
authors.lastname: Kokare
authors.forename: K
authors.initials: K
authors.lastname: Hirani
authors.forename: N K
authors.initials: NK
authors.lastname: Subhedar
authors.forename: C T
authors.initials: CT
authors.lastname: Chopde
authors.forename: R R
authors.initials: RR
authors.lastname: Ugale
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; C092926:BIBP 3226; D009478:Neuropeptide Y; D018341:Receptors, Adrenergic, alpha-2; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D015016:Yohimbine; D000376:Agmatine; D001120:Arginine; D003000:Clonidine