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Interactions of nitric oxide with ?2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.


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 ?-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 ?2 -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.

SUBMITTER: Shelkar GP 

PROVIDER: S-EPMC4978159 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Shelkar Gajanan P GP   Gakare Sukanya G SG   Chakraborty Suwarna S   Dravid Shashank M SM   Ugale Rajesh R RR  

British journal of pharmacology 20160801 17


<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of a  ...[more]

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