Neurokinin₂‐R in medial septum regulate hippocampal and amygdalar ACh release induced by intraseptal application of neurokinins A and B

Abstract

The neurokinin receptors (NK-R), NK(2)- and NK(3)-R, have been implicated in behavioral processes, but apparently in opposite ways: while NK(2)-R agonism disrupts memory and has anxiogenic-like action, NK(3) -R agonists facilitate memory and display anxiolytic-like effects. Systemic application of NK(2)-R antagonists block the release of acetylcholine (ACh) in the hippocampus, which is induced by intraseptal administration of the NK(2)-R ligand, neurokinin A (NKA). We investigated the effects of medial septal injection of NKA and a preferred ligand of NK(3)-R, neurokinin B (NKB), on the activity of cholinergic neurons of the basal forebrain and assessed the role of the medial septal NK(2)-R in the control of extracellular ACh levels in cholinergic projection areas. ACh was dialysed in the frontal cortex, amygdala and hippocampus of anesthetized animals and was analysed by HPLC-EC. ACh levels in hippocampus and amygdala, but not in frontal cortex were increased after intraseptal injection of either NKA or NKB (0.1, 1, 10 μM). Application of the nonpeptidic NK(2)-R antagonist, saredutant SR48968 (1, 10, 100 pM), followed by NKA (1 μM) or NKB (10 μM) injection into the medial septum, blocked the ACh increase in hippocampus and amygdala. These results indicate that medial septal NK(2)-R have an important role in mediating ACh release, for one, via the septal-hippocampal cholinergic projection and, secondly, via direct or indirect route to the amygdala, but not frontal cortex. They also support the hypothesis that hippocampal cholinergic neurotransmission controls amygdala function suggesting that this interaction is regulated via NK(2)-R in the medial septum.

Neurokinin 3 Receptor Effects on Cognitive Behaviour in a Rat Model of Alzheimer's Disease

“…In the open eld test, anxiolytic-like effect was observed with both low dose (0.2 mg/kg) and high dose (0.4 mg/kg) of senktide [20]. In another study, while NK2R agonism has memory loss and anxiogenic effects, NK3R agonists have been reported to show memory-healing and anxiolytic effects [25]. In our project the distance moved, velocity and movement were found to be reduced in the nal measurement values.…”

“…Control animals were injected with solvent. Doses were determined taking into account previous studies that showed a healing effect in learning and memory tests [20,21,25,26,27,28].…”

“…No signi cant effect was seen in the frontal cortex. In the amygdala, there was an insigni cant increase in ACh [25]. The pharmacological stimulation of NK3R has been shown to signi cantly improve learning and memory in older animals.…”

“…ICV senktide administration has also been found to induce anxiolytic-like effect in mice [24]. Based on the systemic and peripheral administration of senktide, it can be concluded that NK3R may have a modulating role in anxiety and learning processes and forebrain cholinergic systems may be likely to participate in these actions [25].…”

Medial septum neurokinin- and somatostatin-sensitive mechanisms mediate sensorimotor and nociceptive behaviours

“…NK2R and NK3R, which modulate their excitability (Chen et al, 2001;de Souza Silva et al, 2013;Morozova et al, 2008;Schäble et al, 2012;Steinberg et al, 1998). Indeed, the NKR are almost exclusively localized to septal cholinergic neurons.…”