Pharmacologically induced cessation of burst activity in nigral dopamine neurons: significance for the terminal dopamine efflux.
Results obtained previously indicate that the firing pattern of midbrain dopamine (DA) neurons is of importance for the terminal DA release. In the present combined electrophysiological and microdialysis study, the influence of the firing pattern on striatal DA release was studied by using the previously observed ability of low doses of gamma-hydroxybutyrate (GHBA) to profoundly regularize the firing pattern of rat DA neurons in the substantia nigra (SN). Administration of GHBA (200 mg/kg, i.v.) did not significantly reduce the firing rate of any of the DA neurons recorded from, but rather caused a slight transient excitation. However, this dose of the drug caused a profound regularization of the firing pattern and abolished burst activity of the DA neurons. The DA concentration in the dialysate obtained from the striatum (10 min sampling periods) decreased with the lowest value (67% of predrug value) observed at the sampling period 20-30 min after the GHBA administration. As a complement to microdialysis, the 3-methoxytyramine (3-MT) accumulation in striatal tissue following monoamine oxidase inhibition was determined as an indirect measure of DA release in vivo. The 3-MT concentrations in the striatum decreased to 84% of controls following 200 mg/kg of GHBA. To exclude an effect on DA release conceivably mediated by GHBA locally in the striatum, GHBA (10(-7)-10(-3) M) was given locally in the dialysis probe and was found to increase DA in the dialysate (maximally to 140% of controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Nissbrandt
H
H
Department of Pharmacology, University of Göteborg, Sweden.
Elverfors
A
A
Engberg
G
G
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D017551:Microdialysis; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D012978:Sodium Oxybate; D004298:Dopamine