Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen.
Rats were treated with desipramine 5 mg/kg, nomifensine 10 mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither 3[H]SCH 23390 nor 3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.
Hilakivi
I
I
Department of Physiology, Institute of Biomedicine, University of Helsinki, Finland.
Ahtee
L
L
Rinne
J O
JO
Taira
T
T
Attila
L M
LM
Marjamaki
P
P
D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D015306:Biogenic Monoamines / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D015031:Zimeldine / Q000494:pharmacology
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D011954:Receptors, Dopamine; D009627:Nomifensine; D015031:Zimeldine; D003891:Desipramine