Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex.
BACKGROUND
Valproic acid (VPA) is a psychoactive drug currently used for the treatment of epilepsy. Recently it has been introduced in psychiatry for the treatment of bipolar disorders, aggression, impulsivity, and resistant schizophrenia, although the mechanism by which VPA acts on these psychiatric diseases remains still unknown.


OBJECTIVE
The aim of this study was to analyze the distinct effects of sodium-(Na-) and magnesium-valproate (Mg-VPA) in pyramidal neurons of the medial prefrontal cortex (mPFC) and their interactions with gamma-aminobutyric acid (GABA) and excitatory amino acid responses.


METHODS
In vivo electrophysiology and microiontophoresis techniques were used to attend these goals.


RESULTS
Both VPA salts decreased spontaneous neuronal firing activity in greater than 60% of recorded pyramidal neurons as well as potentiated GABA inhibitions. When injected at equal concentrations and currents, Mg-VPA blocked the excitatory responses induced by N-methyl-D-aspartate (NMDA) more frequently than Na-VPA. Both VPA salts equally blocked the excitatory responses of quisqualate and kainate.


CONCLUSIONS
These data suggest that VPA salts significantly modulate the activity of excitatory amino acid at mPFC pyramidal neurons and this mechanism should explain the therapeutic effects of valproate in psychiatric diseases involving NMDA, AMPA, and kainate receptors at the mPFC level.
Gobbi
Gabriella
G
Department of Psychiatry, McGill University, Montreal, Quebec, Canada. gabriella.gobbi@mcgill.ca
Janiri
Luigi
L
D000200:Action Potentials; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium; D016202:N-Methylaspartate / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012492:Salts; D012964:Sodium; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000737:chemistry / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D012492:Salts; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D012964:Sodium; D008274:Magnesium; D007608:Kainic Acid