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

Abstract

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.

Effects of Neonatal Clomipramine Treatment on Locomotor Activity, Anxiety-Related Behavior and Serotonin Turnover in Syrian Hamsters

“…Also, an increased 5-HIAA/ 5-HT ratio (an indicator of an increased 5-HT metabolism) was found in the hypothalamus and midbrain raphe of clomipramine-treated hamsters. The results agree with those of a previous study, in which an increased 5-HIAA/ 5-HT index was described in rats neonatally treated with monoamine reuptake inhibitors [10]. Since we previously reported that clomipramine-treated hamsters exhibited an enhanced phase advance of the wheel-running activity rhythm in response to a 5-HT agonist [27], the diminished 5-HT content in projection areas can be interpreted as reflecting an altered serotonergic neurotransmission, per-haps via the up-regulation of 5-HT receptors.…”

“…Altered electrophysiological and electrodermal responses as well as alterations of monoaminergic neurotransmission were also reported [10,[21][22][23]. Such abnormalities were long-lasting and some of them improved after treatment with antidepressants [1].…”

The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring

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“…Postnatal exposure to Zimelidine (SSRI) to rat pups 2–3 weeks after birth significantly increased the 5-HIAA/5-HT ratio in the brain stem and cortex of 2 month old offspring (Hilakivi et al, 1995). In prenatally stressed mice, treatment with fluoxetine during postnatal weeks 1–3 also lowered the 5-HT turnover rate in offspring (Ishiwata et al, 2005).…”