³H‐nicotine‐ and ¹²⁵I‐alpha‐bungarotoxin‐labeled nicotinic receptors in the interpeduncular nucleus of rats. II. Effects of habenular deafferentation

Abstract

The cholinergic innervation of the interpeduncular nucleus (IPN) is wholly extrinsic and is greatly attenuated by bilateral habenular destruction. We describe changes in the labeling of putative nicotinic receptors within this nucleus at 3, 5, or 11 days after bilateral habenular lesions. Adjacent tissue sections of the rat IPN were utilized for 3H-nicotine and 125I-alpha-bungarotoxin (125I-BTX) receptor autoradiography. Compared to sham-operated controls, habenular destruction significantly reduced autoradiographic 3H-nicotine labeling in rostral (-25%), intermediate (-13%), and lateral subnuclei (-36%). Labeling in the central subnucleus was unchanged. Loss of labeling was maximal at the shortest survival time (3 days) and did not change thereafter. In order to establish whether this loss was due to a reduction in the number or the affinity of 3H-nicotine-binding sites, a membrane assay was performed on microdissected IPN tissue from rats that had received surgery 3 days previously. Bilateral habenular lesions produced a 35% reduction of high-affinity 3H-nicotine-binding sites, with no change in binding affinity. Bilateral habenular lesions reduced 125I-BTX labeling in the intermediate subnuclei, and a slight increase occurred in the rostral subnucleus. In the lateral subnuclei, 125I-BTX labeling was significantly reduced (27%) at 3 days but not at later survival times. In view of the known synaptic morphology of the habenulointerpeduncular tract, it is concluded that a subpopulation of 3H-nicotine binding sites within the IPN is located on afferent axons and/or terminals. This subpopulation, located within rostral, intermediate, and lateral subnuclei, may correspond to presynaptic nicotinic cholinergic receptors. Sites that bind 125I-BTX may include a presynaptic subpopulation located in the lateral and possibly the intermediate subnuclei.

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

“…Our analysis further suggests that, in the rat, this association occurs not only in projections from ''relay'' nuclei to neocortex but also in projections from ''association'' nuclei to allocortex. We also show for the first time that the decrease in cortical binding following thalamic lesions is due to a reduction in receptor density (B max ) and not in binding affinity (K D ); both kinds of change have been reported following lesions to other neuronal pathways (Schwartz et al, 1984;Morrow et al, 1985;Clarke et al, 1986). That the decrease in B max was obtained in tissue homogenates further indicates that the loss of autoradiographic labelling was not simply the result of a change in differential quenching by white vs. grey matter (Zilles et al, 1990).…”

Nicotine and tetrahydroaminoacradine: Evidence for improved attention in patients with dementia of the Alzheimer type

“…Nicotine has various and complex actions, and in addition to its conventional post-synaptic action, nicotine may also increase the release of Ach via presynaptic nicotinic autoreceptors [Clarke et al, 1986;Rowell and Winkler, 1984;Araujo et al, 1988;Richard et al, 19881. Newhouse et al [ 19881 administered nicotine intravenously to six DAT patients, and found no improvement in mnemonic function.…”

Tethered Agonist Analogs as Site-Specific Probes for Domains of the Human α7 Nicotinic Acetylcholine Receptor that Differentially Regulate Activation and Desensitization

“…In the brain, heteromeric ␣4␤2-containing and homomeric ␣7 subtypes are the two major types of the nAChRs representing high-affinity binding sites for nicotine and ␣-bungarotoxin, respectively (Clarke et al, 1986;Gotti et al, 2007). Although ␣4␤2 receptors have been strongly associated with the cognitive and addicting effects of nicotine, ␣7 nAChRs have been implicated as influential in neuroprotection (Svensson and Nordberg, 1999), attentional and cognitive enhancement (Young et al, 2004), and the regulation of inflammatory signaling (Wang et al, 2003;Giebelen et al, 2007;Pavlov et al, 2007).…”