Functional mu opioid receptors are expressed in cholinergic interneurons of the rat dorsal striatum: territorial specificity and diurnal variation

Abstract

Striatal cholinergic interneurons play a crucial role in the control of movement as well as in motivational and learning aspects of behaviour. Neuropeptides regulate striatal cholinergic transmission and particularly activation of mu opioid receptor (MOR) inhibits acetylcholine (ACh) release in the dorsal striatum. In the present study we investigated whether this cholinergic transmission could be modulated by an enkephalin/MOR direct process. We show that mRNA and protein of MORs are expressed by cholinergic interneurons in the limbic/prefrontal territory but not by those in the sensorimotor territory of the dorsal striatum. These MORs are functional because potassium-evoked release of ACh from striatal synaptosomes was dose-dependently reduced by a selective MOR agonist, this effect being suppressed by a MOR antagonist. The MOR regulation of cholinergic interneurons presented a diurnal variation. (i) The percentage of cholinergic interneurons containing MORs that was 32% at the beginning of the light period (morning) increased to 80% in the afternoon. (ii) The MOR-mediated inhibition of synaptosomal ACh release was higher in the afternoon than in the morning. (iii) While preproenkephalin mRNA levels remained stable, enkephalin tissue content was the lowest (-32%) in the afternoon when the spontaneous (+35%) and the N-methyl-d-aspartate-evoked (+140%) releases of enkephalin (from microsuperfused slices) were the highest. Therefore, by acting on MORs present on cholinergic interneurons, endogenously released enkephalin reduces ACh release. This direct enkephalin/MOR regulation of cholinergic transmission that operates only in the limbic/prefrontal territory of the dorsal striatum might contribute to information processing in fronto-cortico-basal ganglia circuits.

Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration

“…Although our lesions were targeted to mu opioid receptor-expressing neurons of the rostral patch compartment (Herkenham and Pert, 1981; Pert et al, 1976; Tempel and Zukin, 1987), a very small portion of mu opioid receptors exist on the medium spiny neurons of the matrix compartment (Guttenberg et al, 1996; Kaneko et al, 1995), as well as on a subset of cholinergic interneurons (Jabourian et al, 2005), raising the possibility that regions outside of the patch compartment may have been compromised by DERM-SAP treatment. However, our group and others have previously shown that both the matrix compartment and cholinergic interneurons were unaffected following DERM-SAP treatment (Lawhorn et al, 2009; Murray et al, 2014).…”

Roles of μ-Opioid Receptors in GABAergic Synaptic Transmission in the Striosome and Matrix Compartments of the Striatum

“…Curiously, MOR expression in cholinergic interneurons was far more prominent in the afternoon (80%) than in the morning (32%), so that MOR-mediated synaptosomal release of acetylcholine was higher in the afternoon than in the morning [89]. Endogenous SP thus facilitates acetylcholine release in the morning, while in the afternoon, when MOR expression is high, blockade of MOR is required to observe facilitatory effects of SP on acetylcholine release [90].…”

Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring

“…The lack of effect on locomotion activity seems to be in line with the fact that we have found no changes in the content of the μ-opioid receptor in the adult N offspring. It is well known that the μ-opioid receptor activation in the dorsal striatum indirectly regulates locomotor activity [54].…”