Acute and chronic effects of fluoxetine and haloperidol on mouse brain serotonin and norepinephrine turnover.
Evidence from clinical studies suggests that the noradrenergic system may play a role in the pathophysiology of antidepressant- and neuroleptic-induced akathisia. In limited previous neurochemical research, acute treatment with selective serotonin reuptake inhibitors (SSRIs) has been reported to increase rat brain norepinephrine (NE) turnover or release. We have examined the neurochemical effects of 2 hr, 4 day, and 20 day treatment with the SSRI fluoxetine, and the neuroleptic haloperidol, on regional brain monoamine metabolism. Short and long-term fluoxetine treatment produced substantial decreases (to 65-79% of control) in serotonin (5HT) turnover. However no effects of fluoxetine on mouse brain NE turnover--as assessed by forebrain, hypothalamus, and hindbrain 3-methoxy-4-hydroxyphenylglycol (MHPG) levels or MHPG/NE ratios--were observed. Acute (2 hr) fluoxetine also did not alter regional NE turnover in rat brain. In contrast, haloperidol tended to increase MHPG levels and MHPG/NE ratios in the mouse brain regions studied. The persistence of decreased 5HT turnover during fluoxetine treatment, the lack of an effect of fluoxetine on NE turnover, and the increased NE turnover seen after haloperidol may have important implications regarding drug responsivity and the mechanism of akathisia induction.
Hall
L M
LM
Child Study Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA.
Anderson
G M
GM
Cohen
D J
DJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity
D005473:Fluoxetine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid