Lack of pre-synaptic dopaminergic involvement in modafinil activity in anaesthetized mice: in vivo voltammetry studies.
Modafinil was compared to the indirect dopaminergic drugs, dexamphetamine and methylphenidate, using in vivo differential normal pulse voltammetry with carbon fibre electrodes located in the caudate nucleus to study extracellular catechol level in anaesthetized mice. Modafinil (16-256 mg kg-1) failed to modify the catechol oxidation peak height (peak 2). Dexamphetamine at low doses (2 and 4 mg kg-1) decreased, while at a higher dose (8 mg kg-1) did not modify peak 2 height. A low dose of methylphenidate (16 mg kg-1) did not display any effect, while higher doses (32 and 64 mg kg-1) increased peak 2 height. Pargyline-induced monoamine oxidase inhibition elicited a rapid and dramatic decrease in peak 2 height (related to the decrease of catechol levels). In these conditions modafinil (64 and 256 mg kg-1) did not modify, while dexamphetamine (2, 4 and 8 mg kg-1) and methylphenidate (16, 32 and 64 mg kg-1) increased peak 2 height in relation to synaptic dopamine level increase. This study, in mice, demonstrated the lack of effects of modafinil on nigro-striatal function, at the pre-synaptic level, as opposed to dexamphetamine and methylphenidate.
De Séréville
J E
JE
Centre de Recherches, Maisons-Alfort, France.
Boer
C
C
Rambert
F A
FA
Duteil
J
J
D000758:Anesthesia; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D000077408:Modafinil; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D017661:Receptors, Presynaptic / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D008781:Methyltyrosines; D008996:Monoamine Oxidase Inhibitors; D017661:Receptors, Presynaptic; D008774:Methylphenidate; D019805:alpha-Methyltyrosine; D010293:Pargyline; D014446:Tyrosine 3-Monooxygenase; D000077408:Modafinil; D003913:Dextroamphetamine; D004298:Dopamine