The Role of Substance P in the Marginal Division of the Neostriatum in Learning and Memory is Mediated Through the Neurokinin 1 Receptor in Rats

Abstract

Substance P (SP) is a neuropeptide that plays an important role in inflammation, respiration, pain, aggression, anxiety, and learning and memory mainly through its high affinity neurokinin 1 receptor (NK1R). The marginal division (MrD) is a pan-shaped subdivision in the caudomedial margin of the neostriatum in the mammalian brain and is known to be involved in learning and memory. We studied the expression of SP, NK1R and NK1R mRNA in the rat striatum by immunohistochemistry, immunofluorescence and in situ hybridization, and found that the levels of SP, NK1R protein and NK1R mRNA were high in the cell bodies, fibers and terminals of neurons in the neostriatum, especially in the MrD. Knocking down NK1R activity in the MrD by using an antisense oligonucleotide against NK1R mRNA inhibited learning and memory in a Y-maze behavioral test. Our results show that NK1R mediates the role of SP in the MrD in learning and memory.

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

“…Transgenic mouse models of AD based on the known genetic origins of familial AD have significantly contributed to the understanding of the molecular mechanisms involved in the onset and progression of the disease 52 . Studies using animal models showed that administration of SP provides protection from the cognitive impairment induced by Aβ infusion 53 , prevents Aβ induced neuronal loss 54 and improves memory functions 55 . Despite the observed benefits, it is unlikely that administration of SP will be used as a treatment of AD as it induces multiple effects including risk of emesis and nausea.…”

Antagonism of L-type Cav channels with nifedipine differentially affects performance of wildtype and NK1R−/− mice in the 5-Choice Serial Reaction-Time Task

“…NK1R are expressed on interneurons in the dorsal striatum (Richardson et al, 2000) where they are thought to have a role in synaptic plasticity and learning (Liu et al, 2011). The majority of these NK1R-expressing interneurons are cholinergic (Gerfen, 1991), but some are GABAergic (NPY/somatostatin (SOM)/NOS-expressing) (Kawaguchi et al, 1995;Li et al, 2002).…”

The Marginal Division of the Striatum and Hippocampus Has Different Role and Mechanism in Learning and Memory

“…However, increasing amount of evidence suggests that other brain regions such as the prefrontal cortex, amygdala, limbic system, and BNM are also involved in learn and memory [6–8]. Our previous studies have also identified a new subdivision of the neostriatum, MrD, to be involved in learning and memory, especially in associative learning and declarative memory [10, 19].…”

“…Knocking down NK1R activity in the MrD by using an antisense oligonucleotide against NK1R messenger RNA (mRNA) inhibited learning and memory of rats in a Y-maze behavioral test. Thus, NK1R is likely to mediate the role of the MrD in learning and memory [8]. …”