Interactions of nitric oxide with α2-adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and Purpose: Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. Experimental Approach: The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the α2-adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Key Results: Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. Conclusions and Implications: The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC.

Original languageEnglish (US)
Pages (from-to)2589-2599
Number of pages11
JournalBritish Journal of Pharmacology
DOIs
StatePublished - Sep 1 2016

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Agmatine
Locus Coeruleus
Adrenergic Receptors
Nitric Oxide
Yohimbine
S-Nitrosoglutathione
Dizocilpine Maleate
NG-Nitroarginine Methyl Ester
Tyrosine 3-Monooxygenase
Clonidine
Imidazoline Receptors
Learning
Injections
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Neurotransmitter Agents

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Interactions of nitric oxide with α2-adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine. / Shelkar, Gajanan P.; Gakare, Sukanya G.; Chakraborty, Suwarna; Dravid, Shashank M.; Ugale, Rajesh R.

In: British Journal of Pharmacology, 01.09.2016, p. 2589-2599.

Research output: Contribution to journalArticle

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T1 - Interactions of nitric oxide with α2-adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine

AU - Shelkar, Gajanan P.

AU - Gakare, Sukanya G.

AU - Chakraborty, Suwarna

AU - Dravid, Shashank M.

AU - Ugale, Rajesh R.

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