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

Abstract

BACKGROUND AND PURPOSEAgmatine, 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 APPROACHThe 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 α 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 RESULTSAgmatine (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 IMPLICATIONSThe facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC.

The nucleus locus coeruleus modulatory effect on memory formation: A literature review

“…Similarly, according to Fan et al obtained results of an animal study, corticosterone and stress increase the expression of adrenaline-producing enzymes in LC, boost the function of the basolateral amygdala (BLA) and development of avoidance behavior [15]. Also, Shelkar et al have been reported that interaction between LC-NE and NO facilitates the expression of avoidance behavior [16]. Moreover, Khakpour-Taleghani et al revealed that while temporary LC inactivation has no influence on the acquisition of negative experiences during avoidance learning, LC plays a role in the consolidation of this memory and converting short-term into long-term memory [17].…”

Effects of agmatine on radial‐arm maze memory performance and autistic‐like behaviors in a male rat model of autism

“…Previous studies showed that agmatine facilitates memory retrieval in other memory tasks such as inhibitory avoidance test and MWM in healthy animals or other neurodegenerative disorders such as Alzheimer's disease. Limitations of this study for evaluating the effects of agmatine at the additional doses or number of injections are likely to be one of the causes of controversy with other studies (Dr et al, 2016;Kotagale et al, 2020).…”