Gajanan P Shelkar, Sukanya G Gakare, Suwarna Chakraborty, Shashank M Dravid, Rajesh R Ugale

Agmatine, a putative neurotransmitter plays a vital role in learning and memory. Although, it is considered as endogenous ligand of imidazoline receptors, exhibits high affinity towards α-adrenoceptors (α-ARs), nitric oxide synthase (NOS), and N-methyl-D -aspartic acid (NMDA) receptors. These substrates within locus coeruleus (LC) are critically involved in learning and memory processes. Male Wistar rat were stereotaxicaly cannulated into LC and hippocampus. Different groups were administered with agmatine (i.p./i-LC) to observe its effect on acquisition, consolidation and retrieval of IA memory. NO donor (SNG), non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), α2-AR antagonist (yohimbine), agonist (clonidine) were administered before agmatine in LC. Moreover, influence of intrahippocampal NMDA antagonist, MK-801 was observed on memory enhancing effect of agmatine, SNG and yohimbine. In addition, immunohistochemical expression of TH and eNOS were observed in LC. Agmatine (i-LC/ i.p.) facilitates the retrieval of memory in IA test. S-Nitrosoglutathione potentiated while L-NAME and L-NIO decreased the agmatine's effect in IA test. In contrast, L-NIL and 7-NI does not alter the effect of agmatine. Further, yohimbine potentiated whereas clonidine attenuated effects of agmatine within LC. Moreover, effect of agmatine, SNG and yohimbine was blocked by intrahippocampal administration of NMDA antagonist, MK-801. In addition, agmatine treatment significantly increased the population of TH- as well as eNOS-immunoreactive elements in the LC. Thus results of present study have demonstrated that the facilitation of memory retrieval in IA task by agmatine is probably mediated by eNOS-NO-NE pathway in LC.