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B S Bunney

Publications and source records attributed to B S Bunney.

16 recordsLinked to original sources
PubMed1979

Paradoxical GABA excitation of nigral dopaminergic cells: indirect mediation through reticulata inhibitory neurons.

Biochemical and electrophysiological and electrophysiological studies suggest that GABA agonists increase the activity of dopaminergic neurons in the zona compacta (ZC) of the substantia nigra despite a known GABAergic input to ZC cells. Using single-unit recording techniques we have investigated this "paradoxical" effect. One population of neurons located in the zona reticulata (ZR) of the substantia nigra was found to be 20 times more sensitive to iontophoretically applied GABA than ZC neurons. GABA introduced by means of microiontophoresis into the ZR caused an increase in ZC cell activity while glutamic acid introduced in the same manner produced an inhibition of ZC cells. The latter effect was blocked by low doses of picrotoxin. Muscimol (i.v.) caused a decrease in ZR cell activity at the same dose that caused a parallel increase in ZC cell firing rate. These data suggest that ZC cells receive an inhibitory GABAergic input from ZR cells that are in turn inhibited by low doses of GABA agonists. Such an anatomical arrangement would account for the "paradoxical" excitatory effect of GABA agonists on ZC neuron activity.

Animals↗
PubMed1979

Dopamine auto- and postsynaptic receptors: electrophysiological evidence for differential sensitivity to dopamine agonists.

The responses of dopamine cells in the substantia nigra to iontophoretically administered dopamine and intravenous apomorphine were compared to the responses of spontaneously active neurons in the caudate nucleus. Dopaminergic cells were six to ten times more sensitive to dopamine and intravenous apomorphine than 86 percent of the caudate cells tested. This differential sensitivity of dopamine auto- and postsynaptic receptors may explain the apparently paradoxical behavioral effects induced by small compared to large doses of some dopamine agonists and may provide a means of developing new types of drugs to antagonize dopaminergic influence in the central nervous system.

Action Potentials↗
PubMed1977

Dopamine"autoreceptors": pharmacological characterization by microiontophoretic single cell recording studies.

The effects on the firing of single dopamine (DA) neurons in the substantia nigra (and adjacent ventral tegmental area) of a representative group of catecholamine agonists and antagonists were studied in rats using single cell recording and microiontophoretic techniques. Microiontophoretic application of DA or the DA agonist apomorphine depressed the firing of these cells; the DA antagonist trifluoperazine blocked this effect. However, the alpha-agonist clonidine had no depressant effect and the beta-agonist isoproteronol had only a weak depressant action on DA neurons. Furthermore, the alpha-antagonist piperoxane and the beta-antagonist sotolol were completely ineffective in blocking the depressant effects of DA. These results show that DA-sensitive receptors on the soma of DA neurons are pharmacologically distinct from alpha or beta adrenoreceptors. Because of their location and selective responsiveness to DA agonists, the catecholamine receptors on the soma of DA neurons appear best classified as DA "autoreceptors".

Action Potentials↗
PubMed1976

The precise localization of nigral afferents in the rat as determined by a retrograde tracing technique.

Afferent innervation of the rat substantia nigra (SN) was studied by the retrograde horseradish peroxidase (HRP) method. High concentrations of HRP were deposited in discrete subregions of the SN by means of a microiontophoretic delivery system. Using this technique it was possible to demonstrate that the caudatonigral projection system is arranged topographically; All portions of the caudate-putamen except for a central medial core were found to contain HRP positive cells, indicative of retrograde transport. In the positive areas a much larger percentage of cells (30-50%) were found to participate in this projection than has previously been reported. Only medium size cells (12-20 mum) were found to contain the HRP reaction product. Other areas found to heavily innervate the SN were the globus pallidus, central nucleus of the amygdala and dorsal raphe nucleus. Areas containing fewer reactive cells but which also appear to innervate the SN included the prefrontal cortex and lateral habenula. These results emphasize the importance of striatonigral projections which recent studies have suggested contain a GABAergic link.

Amygdala↗
PubMed1975

Piribedil and apomorphine: pre- and postsynaptic effects on dopamine synthesis and neuronal activity.

Piribedil and apomorphine can cause a complete but temporary inhibition in firing of the DA-containing neurons. The cells recover to approximately 30 to 40% of the original firing rate, and with subsequent administration of the drug become more and more resistant to further inhibition. At this point they are also resistant to inhibition by other direct- or indirect-acting DA agonists that are normally able to inhibit the firing of DA cells. This effect may be due to an interaction of the DA agonists with the postsynaptic DA receptors, but apomorphine at least is able to inhibit the firing of DA cells directly when iontophoresed onto the DA cell body (Aghajanian and Bunney, 1973). These drugs can block the increase in DA synthesis observed in the absence of impulse flow, indicating a presynaptic site of acttion. Taken together, these results suggest that in interpreting the effects of drugs interacting with the DA systems several points of interaction should be considered.

Animals↗