Neurokinin 1 receptor distribution in cholinergic neurons and targets of substance P terminals in the rat nucleus accumbens

Abstract

Substance P (SP) is the major endogenous ligand for neurokinin 1 (NK1) receptors and, together with acetylcholine, has an important role in motivated behaviors involving the limbic shell and motor core of the nucleus accumbens (NAc). To determine the functional sites for SP activation of NK-1 receptors and potential interactions with cholinergic neurons in these regions, the authors examined the electron microscopic immunocytochemical localization either of antisera against the NK1 receptor or of the NK1 receptor and either 1) SP or 2) the vesicular acetylcholine transporter (VAchT) in rat NAc. In both the NAc shell and core, NK1 receptor labeling was localized mainly to somatic and dendritic plasma membranes and nearby endosomal organelles in aspiny neurons. In sections through the ventromedial shell that were processed for NK1/SP labeling, 46% of the NK1-immunoreactive dendrites (n = 603 dendrites) showed symmetric or appositional contacts with SP-containing terminals. These terminals and several others that formed symmetric synapses also occasionally were immunoreactive for NK1 receptors. Analysis of the shell region for NK1/VAchT labeling showed that 61% of the total immunoreactive dendrites (n = 534 dendrites) contained NK1 receptors without VAchT, 29% contained both products, and 10% contained VAchT only. Many of the labeled somata and dendrites also received synaptic contact from VAchT-containing terminals. These findings suggest that, in the NAc, NK1 receptors are recycled through endosomal compartments and play a role in modulating mainly the postsynaptic responses, but also the presynaptic release, of SP and/or inhibitory neurotransmitters onto aspiny interneurons, some of which are cholinergic.

Cholinergic innervation and thalamic input in rat nucleus accumbens

“…Of three receptors in this class, NK1 are the most abundant and show the highest affinity for substance P (Khawaja and Rogers, 1996;Lu et al, 1998;Saria, 1999). NK1 receptors have been localized to the somatic and dendritic membrane of presumptive cholinergic interneurons immunopositive for the acetylcholine vesicular transporter in rat nACb (Pickel et al, 2000). In that same study, it was also demonstrated that substance P positive terminals make symmetrical synapses with these aspiny neurons.…”

Neurokinin 1 Receptors Regulate Morphine-Induced Endocytosis and Desensitization of μ-Opioid Receptors in CNS Neurons

“…It is possible that this reflects developmental differences between our cultures (which are derived from embryonic rats) and adult animals used in previous studies (Pickel et al, 2000; Jabourian et al, 2005). However, we did observe that MORs and NK1Rs are co-expressed in a significant fraction of cultured amygdala neurons.…”

“…The antinociceptive effects of morphine remain intact in NK1R knock-out animals, further supporting the specificity of NK1R function in modulating opiate reward (De Felipe et al, 1998). Moreover, MORs and NK1Rs are highly expressed in several brain regions relevant to reward processing, including the ventral striatum and amygdala (Pickel et al, 2000; Gadd et al, 2003; Nakaya et al, 2004; Jabourian et al, 2005; Poulin et al, 2006). …”

Spatial and intracellular relationships between the α7 nicotinic acetylcholine receptor and the vesicular acetylcholine transporter in the prefrontal cortex of rat and mouse

“…This antiserum shows a specific band at the predicted 70 kDa molecular weight in Western blots of tissue (Brunelli et al, 2005). The VAChT antiserum has been used extensively in electron microscopy studies in the rat to identify cholinergic processes (Garzón and Pickel, 2000, Pickel et al, 2000, Svingos et al, 2001, Towart et al, 2003, Kaplan et al, 2004). …”