Transmitter release patterns of noradrenergic, dopaminergic and cholinergic axons in rabbit brain slices during short pulse trains, and the operation of presynaptic autoreceptors

Abstract

Slices of rabbit brain were field-stimulated either by single electrical pulses or by trains of 4 or 8 pulses at 1 or 100 Hz in order to study transmitter release patterns and the autoinhibition of transmitter release. The slices were preincubated with 3H-noradrenaline (cortex), 3H-dopamine (caudate nucleus) or 3H-choline (caudate nucleus). Slices preincubated with 3H-noradrenaline were superfused with medium containing desipramine 1 mumol/l. The overflow of tritium elicited by single pulses amounted to 0.19% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was similar, whereas that elicited by 4 pulses/100 Hz was 5.1-fold higher. Yohimbine 10-1000 nmol/l increased up to 2.5-fold the overflow evoked by 4 pulses/1 Hz but did not change the overflow evoked by single pulses or 4 pulses/100 Hz. - Slices preincubated with 3H-dopamine were superfused with medium containing nomifensine 1 mumol/l. The overflow of tritium elicited by single pulses was 0.39% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was 1.3-fold and the overflow elicited by 4 pulses/100 Hz 1.4-fold higher. Domperidone 1-100 nmol/l and sulpiride 10-1000 nmol/l increased up to 2.4-fold the overflow evoked by 4 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 4 pulses/100 Hz. - Slices preincubated with 3H-choline were superfused either with physostigmine-free medium or with medium containing physostigmine 1 mumol/l. In physostigmine-free medium, atropine did not increase the evoked overflow of tritium at any stimulation condition. In physostigmine-containing medium, the overflow elicited by single pulses was 0.18% of the tritium content of the tissue. The overflow elicited by 8 pulses/1 Hz was 2.0-fold and the overflow elicited by 8 pulses/100 Hz 2.2-fold higher. Atropine 2-200 nmol/l increased up to 2.4-fold the overflow evoked by 8 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 8 pulses/100 Hz. In physostigmine-free medium, sulpiride 10-1000 nmol/l did not change the single-pulse-evoked overflow of tritium in the absence but increased it in the presence of nomifensine 1 mumol/l. Single pulses elicit a large release of 3H-noradrenaline, 3H-dopamine and 3H-acetylcholine under the conditions of these experiments. Release elicited by single pulses is not subject to autoinhibition except for a small inhibition by spontaneously released transmitter in the case of dopaminergic and cholinergic axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain

“…This well-documented effect is due to blockade of autoreceptors receptors that normally inhibit release when activated by dopamine (Starke, 1989). The short duration of the pl P (30 msec) gives insufficient time for dopamine autoreceptors to function between pulses (Mayer et al, 1988;Singer, 1988 transmission at the neuromuscular junction differ greatly in that the dopamine released into the synaptic cleft seems destined for extrasynaptic space.…”

“…In the case of the uptake transporter, the rapid binding rate calculated above and the absence of effect of uptake inhibitors on dopamine efflux lead us to predict that a significant fraction of the uptake sites are extrasynaptic as is found in cultured fetal dopamine neurons (Cerrutti et al, 1991). Since the complete development of dopamine autoreceptor inhibition occurs in the 40-100 msec range (Mayer et al, 1988;Singer, 1988;Kennedy et al, 1992) which indicates that autoreceptors have sufficiently fast binding kinetics to buffer efflux from the synaptic cleft, the failure to alter dopamine efflux with a D, antagonist also suggests an extrasynaptic location for dopamine autoreceptors. Indeed, recent anatomical evidence supports an extrasynaptic location for some D, receptors in the rat striatum (Levey et al, 1993;Sesack et al, 1994).…”

“…In the following experiments, we examine dopamine release evoked by one stimulus pulse (1 P) and four stimulus pulses delivered within 30 msec. The latter "pseudo-one-pulse" (plP) should provide insufficient time for dopamine receptors and uptake transporters to function between pulses, although binding to these sites is not precluded (Mayer et al, 1988;Singer, 1988).…”

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

“…However, a train of pulses is necessary to obtain measurable amounts of [DA] o from somatodendritic regions in this system . Short high-frequency trains, or "pseudo-one pulse" stimulations (Յ 100 msec; see also Palij and Stamford, 1993), offer a compromise to a single pulse whereby high transmitter efflux is evoked but in a period of time too short to activate the DA autoreceptor (Mayer et al, 1988;Singer, 1988).…”

Tacrine Increases Stimulation-Evoked Acetylcholine Release from Rat Hippocampal Slices

“…Due to its anticholinesterase activity, tacrine should increase the extracellular concen tration of acetylcholine (ACh), like other cholinesterase inhibitors. It has been found that an increase in the ex tracellular concentration of ACh, or application of mus carinic agonists, inhibits ACh release from the nerve ter minal (11,12). Previous researchers have reported that tacrine inhibits depolarization-induced ACh release (13,14), although these observations would be against the clinical usefulness of tacrine.…”