Effects of Nucleus Basalis Lesions on the Muscarinic and Nicotinic Modulation of [³H] Acetylcholine Release in the Rat Cerebral Cortex

Abstract

Presynaptic muscarinic and nicotinic receptors in the cerebral cortex reportedly inhibit and increase acetylcholine (ACh) release, respectively. In this study, we investigated whether these receptors reside on cholinergic nerve terminals projecting to the cerebral cortex from the nucleus basalis magnocellularis (nbm). Adult male rats received unilateral infusions of ibotenic acid (5 micrograms/1 microliter) in the nbm. Two weeks later, cerebral cortical cholinergic markers (choline acetyltransferase activity, high-affinity choline uptake, and coupled ACh synthesis) were significantly reduced in synaptosomes prepared from the lesioned hemispheres compared to contralateral controls. The depolarization-induced release of [3H]ACh from these synaptosomes was also reduced in the lesioned hemispheres, reflecting the reduced synthesis of transmitter. However, the nbm lesions had no effect on the inhibition of release induced by 100 microM oxotremorine. Synaptosomal [3H]ACh release was not altered by nicotine or the nicotinic agonists anabaseine and 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine. Nicotine (10-100 microM) did increase [3H]ACh release in control and lesioned hemispheres in cortical minces, but to a similar extent. These results suggest that neither muscarinic nor nicotinic receptors modulating ACh release reside on nbm-cholinergic terminals.

Cholinergic receptors in human brain: Effects of aging and alzheimer disease

“…Lesions of the nucleus basalis in rats, aimed to mimic the cholinergic denervation in AD, did not produce significant changes in nAChR binding sites, with the exception of a decrease of a-BTX binding sites (Downen et al, 1989), whereas ChAT activity was severely affected (Atack et al. 1989;Meyer et al, 1987;Wenk and Rokaeus, 1988;Downen et al, 1989). Therefore, these data do not support the suggestion that all cortical AChRs are located on presynaptic cholinergic axons in rat cortex.…”

Effect of acute and subchronic nicotine treatment on cortical acetylcholine release and on nicotinic receptors in rats and guinea‐pigs

“…It has been suggested that this latter type of receptors might be present on the intracortical cholinergic nerve endings (Rowell & Winkler, 1984;Araujo et al, 1987). However, the antagonism by tetrodotoxin of the effect of nicotine on unstimulated guinea-pig cortical slices (Beani et al, 1985), together with some negative results on binding and biochemical studies on synaptosomes after lesioning of the subcortical cholinergic nuclei of the rat (Schwartz et al, 1984;Meyer et al, 1987), cast some doubts about such definite or exclusive localization. Further studies are needed to clarify if these supposed autoreceptors are also upstream (i.e.…”

A population of nicotinic receptors is associated with thalamocortical afferents in the adult rat: Laminal and areal analysis

“…However, experimental lesions of the basal forebrain have produced little or no detectable reduction in cortical 3 H-nicotine or nicotinic 3 H-ACh binding in most published studies (Schwartz et al, 1984;Vige and Briley, 1988;Wenk and Rokaeus, 1988;Tilson et al, 1989;Miyai et al, 1990;Rossner et al, 1995; but see Abdulla et al, 1995). Furthermore, such nicotinic autoreceptors as do exist in the rat cerebral cortex do not appear to be associated with basal forebrain efferents (Meyer et al, 1987).…”