Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats

Hilakivi, Leena A.; Stenberg, Dag; Sinclair, John; Kiianmaa, Kalervo

doi:10.1007/bf00216004

Cited by 36 publications

(20 citation statements)

References 39 publications

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“…The neonatal clomipramine administration has been reported to produce a lifelong increase in REM sleep, impaired sexual activity and diminished aggressive behavior in mature rats (Mirmiran et al, 1981;Hilakivi et al, 1987;Vogel et al, 1988). These abnormalities are analogous to that frequently seen in humans with endogenous depression.…”

Section: Discussionmentioning

confidence: 78%

Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats

Ogawa

Murakami

Kuroda

et al. 1994

J. Neural Transmission

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The aim of the present study is to investigate the effect of neonatal alterations in 5-HT signalling on the regulation of endocrine stress response in adult rats. The neonatal blockade of 5-HT transmission by 5,7-DHT or ritanserin treatment did not alter the density of glucocorticoid receptor (GR) binding sites in the hippocampus, although a 5,7-DHT-induced lesion was clearly shown to decrease in 5-HT content by greater than 80% in the hippocampus. In addition, the animals pretreated with the blockade of 5-HT transmission during early life did not exhibit a hyperresponsiveness of the adrenocortical response to stress. On the other hand, the neonatal administration of the 5-HT uptake inhibitor, clomipramine, was shown to lower the stress responsiveness of the adrenocortical axis in adulthood.

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Section: Discussionmentioning

confidence: 78%

Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats

Ogawa

Murakami

Kuroda

et al. 1994

J. Neural Transmission

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“…This is certainly not the first study to evaluate changes in the serotonin system following neonatal antidepressant treatment. Previous studies have shown that following neonatal exposure to clomipramine, zimelidine, or desipramine, several brain regions in adult rats exhibit reductions in extracellular concentrations of serotonin (Hilakivi et al, 1987b;Feenstra et al, 1996;Vijayakumar and Meti, 1999). Moreover, early administration of clomipramine or Lu-10-134C, a putative SSRI, produces a downregulation of DR SERT mRNA levels in adult rats (Hansen and Mikkelsen, 1998), and in some cases reduces the baseline firing rate of DR neurons (Kinney et al, 1997).…”

Section: Discussionmentioning

confidence: 97%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

274

275

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A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

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“…In all brain parts studied the concentrations of dopamine and its metabolites were about similar in the nomifensine-treated and in the control rats, whereas in the previous study (Hilakivi et al, 1987) the concentration of dopamine was reduced by neonatal treatment with zimeldine and desipramine in the hypothalamus, and in the case of zimeldine also in the neostriatum and limbic forebrain. Turnover of dopamine in the nomifensine rats in the present study, however, tended to be decreased in the neostriatum and tl~e limbic forebrain as shown by decreased DOPAC/DA ratios.…”

Section: Discussionmentioning

confidence: 77%

“…In earlier studies neonatal active sleep was also found to be reduced by early desipramine, zimeldine (Hilakivi et al, 1987) and clomipramine (Mirmiran et al, 1981) exposures. The amount of quiet state, however, was increased by desipramine and zimeldine exposures, and clomipramine did not affect it.…”

Section: Discussionmentioning

confidence: 85%

“…The clomipramine and zimeldine rats were also more active and responded with a decrease in ambulation to a small dose of alcohol in the open-field. Moreover, the neonatal drug treatments caused long-lasting alterations of cerebral monoamine concentrations (Hilakivi et al, 1987). Desipramine preferentially inhibits the uptake of noradrenaline, while clomipramine and zimeldine are preferential 5-hydroxytryptamine (5-HT) uptake inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats

Hilakivi

Ahtee

et al. 1987

J. Neural Transmission

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The aim of the study was to examine the effects of early postnatal exposure to nomifensine, an inhibitor of catecholamine uptake, on concurrent active (REM) sleep, on later alcohol related behavior and on monoamine concentrations in various brain regions of rats. For these purposes rats were given daily injections of 10 mg/kg nomifensine s.c. between the 7th and the 18th postnatal days. During the nomifensine exposure active sleep, expressed as a percentage of total sleeping time, was reduced. At one month of age, the nomifensine rats showed increased ambulation and had lower defecation scores in the open-field than the controls. Neonatal exposure to nomifensine increased voluntary intake of 10% (v/v) alcohol when the rats were 2-3 months of age. The rats, however, did not exhibit preservation in the T-maze, and similarly to control rats suppressed drinking 0.1 M lithium chloride even when thirsty. Measurement of cerebral monoamine concentrations at the age of 3 months suggested that neonatal nomifensine treatment interferes with the noradrenergic and serotonergic systems in several regions of the brain. Concentrations of noradrenaline and 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the cerebral cortex and frontal cortex, concentration of 5-HIAA was decreased in the neostriatum, and concentrations of noradrenaline, 5-hydroxytryptamine (5-HT) and 5-HIAA were elevated in the lower brain stem. Taken together, these findings show that exposure to nomifensine during the 2nd and 3rd postnatal weeks suppresses neonatal active sleep, causes changes in the adult open-field behavior, and increases voluntary alcohol intake, perhaps due to a long-lasting alteration in brain monoamines.

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Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats

Cited by 36 publications

References 39 publications

Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats

Effects of the altered serotonergic signalling by neonatal treatment with 5,7-dihydroxytryptamine, ritanserin or clomipramine on the adrenocortical stress response and the glucocorticoid receptor binding in the hippocampus in adult rats

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats

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