Lithium and valproate attenuate dextroamphetamine-induced changes in brain activation.

Area of Science:

• Neuroscience
• Psychopharmacology

Background:

• Previous research suggests lithium and valproate impact the phosphoinositol (PI) cycle.
• Dextroamphetamine is known to modulate PI cycle activity.
• Dextroamphetamine administration causes task- and region-dependent decreases in brain activation in healthy individuals.

Purpose of the Study:

• To investigate the effects of 14-day pretreatment with lithium and valproate on dextroamphetamine-induced changes in regional brain activity.
• To assess if lithium and valproate can modulate dextroamphetamine's effects on brain activation patterns.

Main Methods:

• A double-blind, placebo-controlled study involving healthy volunteers.
• Participants received sodium valproate (n=12), lithium (n=9), or placebo (n=12) for 14 days.
• Functional magnetic resonance imaging (fMRI) was used to measure brain activity during cognitive tasks before and after dextroamphetamine administration.

Main Results:

• Dextroamphetamine administration consistently decreased regional brain activation across all tasks.
• Lithium pretreatment attenuated dextroamphetamine-induced changes in word generation and spatial attention tasks.
• Valproate pretreatment attenuated dextroamphetamine-induced changes in the working memory task.

Conclusions:

• Lithium and valproate can significantly attenuate dextroamphetamine-induced brain activity changes in a task- and region-specific manner.
• This study provides the first human evidence suggesting lithium and valproate may exert similar effects on regional brain activation.
• These modulatory effects could be mediated by shared mechanisms involving the PI cycle.