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  • Postnatal treatment  (3)
  • Carbon monoxide  (2)
  • Cytotoxicity  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Postnatal treatment ; Long term behavioural and biochemical effects ; GABA-benzodiazepine receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The long term behavioural and biochemical effects of chronic chlordiazepoxide treatment during the period of neuronal maturation in the rat have been investigated. The administration to lactating mothers of chlordiazepoxide at very low doses (0.22 and 2.6 mg/kg) in their drinking water affects both behavioural and biochemical parameters in offspring at 60 days of age and undrugged since weaning. A deficit in the acquisition of the conditioned avoidance response in treated rats was observed, although no significant difference in spontaneous locomotor activity between control and treated rats was found. 3H-Flunitrazepam binding sites in cerebral cortex and hippocampus were decreased by the treatment, whereas no change was detected in cerebellum. Moreover, 3H-muscimol binding sites increased in hippocampus with no changes in cerebral cortex and cerebellum. According to the different regional distribution of benzodiazepine type 1 and type 2 receptors, we suggest that type 2 receptors are selectively affected by the treatment, and that the GABA ergic receptor system is also permanently altered by administration of chlordiazepoxide during early postnatal life.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Postnatal treatment ; Haloperidol ; Apomorphine ; Stereotyped behaviour ; Locomotion ; Learning ; DOPAC ; HVA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were administered 0.5 mg/kg SC of haloperidol (H) or saline (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with H or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and H-pretreated rats were investigated. The intensity of apomorphine (0.5–1 mg/kg, SC)-induced stereotyped behaviour was significantly greater in the H-pretreated group than in S-pretreated animals and this was accompanied by a much more marked reduction of locomotor activity in H-pretreated than in S-pretreated rats. Finally, at 80 days of age (60 days after the postnatal treatment with H or S was interrupted) rats were subjected to a Differential Reinforcement of Low Rates schedule (DRL 15-s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf≤2.5) was significantly more rapid in S-pretreated rats than in H-pretreated ones. In parallel biochemical experiments, acute H produced smaller increases in dopamine turnover in chronic H-treated rats compared with S-treated controls. These data indicate that H treatment in neonatal rats induces behavioural and biochemical changes which can be observed up to 60 days after H withdrawal.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Postnatal treatment ; Clozapine ; Apomorphine ; Stereotyped behaviour ; Locomotion ; Learning ; HVA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S-and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5–1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf≤2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Carbon monoxide ; Prenatal exposure ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) significantly impairs the acquisition of a two-way active avoidance task in 3-month-old male rats as well as the acquisition and reacquisition of this schedule in 18-month-old animals subjected to six daily 20-trial sessions. These deficits do not seem to be attributable to alterations of a non-associative nature, as the intertrial activity and the escape response latencies in CO exposed animals were not significantly affected with respect to controls. These findings, showing that gestational exposure to CO induces in rat offspring permanent learning and memory impairment, confirm that the offspring of smoking mothers may be at considerably greater risk than current epidemiological studies on birthweight and neonatal mortality suggest.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0738
    Keywords: Developmental toxicity ; Carbon monoxide ; Peripheral nerve activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h∞ (V), showed that the percentage of the maximum number of activatable Na channels at the normal resting potential (−80 mV) was increased to ≈85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel development.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0738
    Keywords: Key words Capsaicin ; Capsazepine ; Ruthenium red ; Cytotoxicity ; Vero cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Capsaicin is a natural product of Capsicum peppers, excitatory effects of which have been shown to be mediated by the recently cloned vanilloid receptor 1 (VR1). Since previous studies have shown that capsaicin inhibits protein synthesis, experiments were performed to investigate whether this effect is mediated by VR1 receptor on cultured monkey kidney cells (Vero cells). The capsaicin uptake was assessed in cellular homogenate and in medium by high-performance liquid chromatography (HPLC) separation and quantification on C18 reverse-phase column and fluorescence detection. Toxic effects were assessed by incorporation of [3H]L-leucine into cellular proteins in the presence of capsazepine, the VR1 vanilloid receptor antagonist and Ruthenium red or tyrosine or calcium. Capsazepine (1 to 256 μM) did not modify the uptake rate of capsaicin for incubation times up to 24 h and did not antagonize capsaicin-induced protein synthesis inhibition. It rather inhibited protein synthesis per se from 100 to 256 μM. Ruthenium red which blocks mitochondrial calcium uptake, inhibited protein synthesis and did not antagonise or increase synergistically the effects of capsaicin. Interestingly in a medium deprived of calcium and supplemented by calcium chloride (10–50 μM) the protein synthesis inhibition induced by capsaicin is antagonised somehow. There was no prevention of capsaicin diffusion into the cells. Tyrosine, which seems to be the best preventive agent of capsaicin inhibitory effects, prevents its metabolism but not its diffusion. Capsaicin might enter cells by diffusion and interfere with protein synthesis machinery by competition with tyrosine which in turn prevents the metabolism of capsaicin. The results of the present study suggest that cell responses to capsaicin may be transduced through at least two molecular pathways, one involving VR1, since the receptor antagonist capsazepine fails to prevent the inhibitory effect of capsaicin in Vero cells of renal origin.
    Type of Medium: Electronic Resource
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