Chemical transmission in the rat interpeduncular nucleus in vitro.

Abstract

SUMMARY1. We have used a rat brain-slice preparation to study the effects of some cholinomimetic and amino acid agonists and antagonists on the discharge frequency of neurones in the interpeduncular nucleus (i.p.n.), and on the response of these neurones to electrical stimulation of their main excitatory input, the fasciculus retroflexus of Meynert (f.r.m.).2. A high proportion of i.p.n. neurones were excited by carbachol, acetylcholine (ACh) and muscarine, but methacholine was less effective. The amino acids L-glutamate and L-aspartate were highly effective stimulants of i.p.n. neurones.3. The responses to ACh or carbachol were greatly reduced by the nicotinic blocking agents hexamethonium, d-tubocurarine and mecamylamine but only slightly reduced by atropine. The response to muscarine was abolished by low doses of atropine. a-Bungarotoxin did not block the response of i.p.n. neurones to f.r.m. stimulation or to cholinomimetic agonists. 4. The response of i.p.n. neurones to f.r.m. stimulation was not appreciably affected by high doses of nicotinic antagonists or atropine nor was there any enhancement of the response by physostigmine.5. The amino acid antagonists y-D-glutamylglycine (yDGG) and 2-aminophosphonovalerate (2-APV) were effective blockers ofthe response to f.r.m. stimulation and preferentially reduced responses to aspartate while having little effect on responses to glutamate or cholinomimetic agonists.6. It is concluded that ACh is an unlikely candidate for transmitter in this pathway despite abundant neurochemical evidence in its favour. It is more likely that the transmitter is an excitatory amino acid, probably an aspartate-like substance.

Pharmacological properties of immuno-isolated neuronal nicotinic receptors

“…As others have previously noted, there is a puzzling discrepancy between (1) the relatively high affinity of the cholinergic agonists compared to their concentration required for stimulation in the CNS (Brown et al, 1983), and (2) the relatively low affinities of antagonists such as hexamethonium and mecamylamine, which act on the CNS nicotinic AChR at relatively low concentrations (Brown et al, 1983;Clarke et al, 1985b). In Torpedo electric organ, bound agonist induces conversion of AChR from a low-to high-affinity desensitized form (for review, see Anholt et al, 1985;Popot and Changeux, 1984).…”

Blockade of nicotinic responses by physostigmine, tacrine and other cholinesterase inhibitors in rat striatum

“…However, studies in which physostigmine has been applied directly to this area" have emphasized a muscarinic component (Winn et al, 1983;Smelik & Ernst, 1966). (4) Use of physostigmine perhaps' also helps to account for the surprising absence of demonstrable nicotinic cholinergic transmission reported in the interpeduncular nucleus (Brown et al, 1983).…”

The action of cholinomimetic substances on impulse conduction in the habenulointerpeduncular pathway of the rat in vitro.

“…Although direct transmission from fasciculus retroflexus fibres to interpeduncular neurones in this slice preparation may be mediated by an aspartate-like substance (Brown et al 1983), biochemical and histological evidence suggests a strong cholinergic component to the fasciculus retroflexus (for references see Brown et al 1983) and ACh release following activation of fascicular fibres (by stimulation of the habenular nuclei) has been demonstrated (Sastry, Zialkowske, Hansen, Kavanagh & Evoy, 1979). This raises the question as to whether the nicotinic cholinergic receptors on the fibre terminals might be activated by ACh released from fascicular fibres when they are stimulated thereby producing a degree of feed-back inhibition.…”

“…to stimulation of their afferent input in the fasciculus retroflexus of Meynert recorded in a transverse slice preparation of the rat brain (Brown, Docherty & Halliwell, 1983). These neurones were readily excited by nicotinic cholinomimetic drugs, applied either ionophoretically or by bath perfusion.…”