Effects of Neurotropic Drugs on Brain Cell Replication in vivo and in vitro

Patel, Ambrish J.; Barochovsky, O.; Borges, Swanny Ferreira; Lewis, Paul D.

doi:10.1159/000406882

Cited by 7 publications

(8 citation statements)

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“…Recently we have investigated in-vitro system the role of a number of psychotropic drugs, including haloperidol, in the regulation of cell replication using morphologically preserved brain slices (Barochovsky & Patel, 1981). In agreement with the present in-vivo observations, haloperidol resulted in a dose-dependent reduction in the in-vitro rate of DNA synthesis and a half maximal effect was obtained at a concentration of about 150 ,ug/ml (Barochovsky & Patel, 1981;.…”

Section: Discussionsupporting

confidence: 89%

“…In experimental animals, exposure to drugs acting on the central nervous system during the period of rapid brain development has been shown to result in persistent behavioural changes in later life (Werboff & Gottlieb, 1963;Barlow & Sullivan, 1975;Coyle, Wayner & Singer, 1976;Lundborg & Engel, 1978;Vorhees, Brunner & Butcher, 1979). Previous studies in our laboratories suggested that some of these drugs are capable of disturbing cell proliferation (for reviews see Patel, Barochovsky & Lewis, 1981). Reserpine and chlorpromazine, two of the psychotropic drugs which have been studied in detail caused a severe depression in the in-vivo rate of [3H] thymidine incorporation into DNA of the forebrain and the cerebellum when administered to ll-day-old rats, suggesting a reduction in the rate of cell replication Patel, Bailey & Baliizs, 1979a, Patel et al, 1980.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Haloperidol on Cell Proliferation in the Early Postnatal Rat Brain

Backhouse

Barochovsky

Malik

et al. 1982

Neuropathology Appl Neurobio

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Haloperidol, a widely used neuroleptic, produced a significant depression of the rate of [3H]thymidine incorporation into the DNA of 11-day-old rat brain. The reduction of in-vivo DNA synthesis rate was detectable by 4 h after subcutaneous injection of a single dose of haloperidol (20 mg/kg) and through the period 10-24 h after drug treatment the rate was less than 50% of that of controls in the forebrain. [3H]Thymidine incorporation returned to control values by 32 h. The effect on the cerebellum was similar but less pronounced. The depression was dose-dependent and a half-maximal effect was produced with haloperidol doses of 5-10 mg/kg. Parallel histological studies on treated rats suggested prolongation of the DNA synthesis phase of the cell cycle in the forebrain subependymal layer, associated with an increase in turnover time of about 15%.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Effects of Haloperidol on Cell Proliferation in the Early Postnatal Rat Brain

Backhouse

Barochovsky

Malik

et al. 1982

Neuropathology Appl Neurobio

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“…Treatment of pregnant rats with haloperidol results in low birthweight pups, stunted growth, and reduced brain size [20] that persists through adulthood [21]. Findings of reduced numbers of proliferating neurons in newborn rats exposed in utero to antipsychotic drug are consistent with this overall picture [22]. Furthermore, prenatal drug exposure in rats leads to a reduction in nerve growth factor (NGF) protein and mRNA [23], and a significant decrease in expression of genes involved in neuronal plasticity (including calmodulin) in neonatal brain [24].…”

Section: Introductionmentioning

confidence: 59%

Antipsychotic drugs disrupt normal development in Caenorhabditis elegans via additional mechanisms besides dopamine and serotonin receptors

Donohoe¹,

Aamodt²,

Osborn³

et al. 2006

Pharmacological Research

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Antipsychotic drugs may produce adverse effects during development in humans and rodents. However, the extent of these effects has not been systematically characterized nor have molecular mechanisms been identified. Consequently, we sought to evaluate the effects of an extensive panel of antipsychotic drugs in a model organism, C. elegans, whose development is well characterized, and which offers the possibility of identifying novel molecular targets. For these studies, animals were grown from hatching in the presence of vehicle (control) or antipsychotic drugs over a range of concentrations (20-160 μM) and growth was analyzed by measuring head-to-tail length at various intervals. First-generation antipsychotics (e.g., fluphenazine) generally slowed growth and maturation more than second-generation drugs such as quetiapine, and olanzapine. This is consistent with in vitro effects on human neuronal cell lines. Clozapine, a second-generation drug, produced similar growth deficits as haloperidol. Converging lines of evidence, including the failure to rescue growth with high concentrations of agonists, suggested that the drug-induced delay in development was not mediated by the major neurotransmitter receptors recognized by the antipsychotic drugs. Moreover, in serotonin-deficient tph-1 mutants, the drugs dramatically slowed development and led to larval arrest (including dauer formation), and neuronal abnormalities. Evaluation of alternative targets of the antipsychotics revealed a potential role for calmodulin and underscored the significance of Ca 2+ -calmodulin signaling in development. These findings suggest that antipsychotic drugs may interfere with normal developmental processes, and provide a tool for investigating the key signaling pathways involved.

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“…Neutrotransmitters are involved in the process of sexual differentiation of the central nervous system and mediate the organizing effects of gonadal steroids. Compounds which influence adrenergic, cholinergic or serotoninergic activity in the postnatal period were shown to induce permanent changes in differentiation of the gonadotropin secretion pattern and of sexual behavior in rats (Jarzab et al, 1984;Sickmöller et. al., 1985).…”

Section: Introductionmentioning

confidence: 99%

Influence of Neurotransmitters on Sexual Differentiation of Brain Structure and Function

Döhler¹,

Jarząb²,

Sickmöller³

et al. 2009

Exp Clin Endocrinol Diabetes

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Newborn rats received daily subcutaneous treatment with compounds which influence serotoninergic, cholinergic, alpha-adrenergic and beta-adrenergic activity. In adulthood luteinizing hormone (LH) secretion pattern, female sexual behavior, and the volume of the sexually dimorphic nucleus of the preoptic are (SDN-POA) were determined. Postnatal administration of l-tryptophan increased the volume of the SDN-POA significantly when given alone or when given simultaneously with testosterone propionate (TP). Para-chlorophenyl-alanine (pCPA) also increased SDN-POA volume, but did not potentiate the stimulating influence of TP. Clonidine had no effect per se on SDN-POA development, but it significantly potentiated the effect of TP in females. Salbutamol increased SDN-POA volume in females and in males. Postnatal treatment of female rats with the alpha-adrenergic receptor antagonists prazosine and yohimbine or with the nicotin receptor antagonist mecamylamine had permanent potentiating effects on the pattern of LH secretion, whereas postnatal treatment with beta-adrenergic compounds reduced the LH-release response to gonadal steroids in adulthood. Postnatal treatment with clonidin or l-tryptophane inhibited differentiation of the capacity for lordosis behavior. Beta-receptor agonists postnatally had a potentiating effect on the capacity for lordosis behavior in female and male rats. Cholinergic stimulation postnatally inhibited differentiation of the capacity for lordosis behavior in female rats, but prevented the inhibitory effect of postnatal androgenization. There was no correlation between SDN-POA volume and any of the two functional parameters.

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Effects of Neurotropic Drugs on Brain Cell Replication in vivo and in vitro

Cited by 7 publications

References 0 publications

Effects of Haloperidol on Cell Proliferation in the Early Postnatal Rat Brain

Effects of Haloperidol on Cell Proliferation in the Early Postnatal Rat Brain

Antipsychotic drugs disrupt normal development in Caenorhabditis elegans via additional mechanisms besides dopamine and serotonin receptors

Influence of Neurotransmitters on Sexual Differentiation of Brain Structure and Function

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