Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study.
1 The effects of the inhibition of monoamine oxidase (MAO) type A and B have been evaluated on the spontaneous firing activity of the dopaminergic (principal) neurones of the rat midbrain intracellularly recorded from a slice preparation. 2 The non-specific MAO inhibitor, pargyline, superfused at a concentration of 10-100 microM, decreased or abolished the spontaneous firing discharge of the principal neurons in the subtantia nigra pars compacta and ventral tegmental area. This effect had a slow onset and appeared to be sustained. 3 The administration of the dopamine D2/3 receptor antagonist, sulpiride (100-300 nM), antagonized the pargyline-induced effect, while the superfusion of the dopamine D1 receptor antagonist, SCH 23390 (1-3 microM) did not counteract the induced inhibition of the firing rate. 4 The inhibitor for the MAO A, clorgyline (30-100 microM), reduced the firing rate of the dopaminergic neurones. A similar depressant effect was also observed when a MAO B inhibitor, deprenyl (30-100 microM), was applied. Lower concentrations of both drugs (300 nM-10 microM) did not produce consistent effects on neuronal discharge. 5 Our data suggest that only the blockade of both types of MAO enzymes favours the inhibitory action of endogenous dopamine on somato-dendritic D2/3 autoreceptors.
Mercuri
N B
NB
Dip. Sanita' Pubblica, Universita' di Roma Tor Vergata, Italy.
Bonci
A
A
Siniscalchi
A
A
Stefani
A
A
Calabresi
P
P
Bernardi
G
G
D000818:Animals; D003010:Clorgyline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010293:Pargyline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects
D018492:Dopamine Antagonists; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D010293:Pargyline; D003010:Clorgyline; D004298:Dopamine