Antidepressant-like and antinociceptive-like actions of 4-(4'-chlorophenyl)-6-(4''-methylphenyl)-2-hydrazinepyrimidine Mannich base in mice.

This study investigated the possible antidepressant and antinociceptive action of CPMPH Mannich base, as well as the involvement of serotonergic, dopaminergic, noradrenergic and opioid systems and the L-arginine-nitric oxide pathway in the antidepressant-like effect of CPMPH in the forced swimming test (FST) in mice. The immobility time in the FST was significantly reduced by CPMPH (0.1-10 mg/kg, i.p.), without accompanying changes in the ambulation in an open-field. CPMPH at high doses (i.p. or s.c. routes) produced a significant inhibition of acetic acid-induced writhing. The antidepressant-like effect of CPMPH (1 mg/kg, i.p.) in the FST was prevented by pre-treatment of mice with methysergide (2 mg/kg, i.p., a non-selective serotonin receptor antagonist), sulpiride (32 mg/kg, i.p., a D2 receptor antagonist) or yohimbine (1 mg/kg, i.p., an alpha2-adrenoceptor antagonist). In contrast, the antidepressant-like effect of CPMPH was not affected by pre-treatment (i.p.) with naloxone (1 mg/kg, a non-selective opioid receptor antagonist) or L-arginine (750 mg/kg, a nitric oxide precursor). The results demonstrate that CPMPH had an antidepressant-like action that appears to be mediated through its interaction with serotonergic, dopaminergic and noradrenergic systems.

Effects of lead and/or zinc exposure during the second stage of rapid postnatal brain growth on delta-aminolevulinate dehydratase and negative geotaxis of suckling rats

Lead has been shown to produce cognitive and motor deficits in young rats that could be mediated, at least in part, by inhibition of the zinc-containing heme biosynthetic enzyme delta-aminolevulinate dehydratase (ALA-D). In the present study we investigated the effects of lead and/or zinc treatment during the second stage of rapid postnatal brain development on brain, kidney and blood ALA-D specific activity, as well as the negative geotaxis behavior of rats. Eight-day-old Wistar rats were injected intraperitoneally with saline, lead acetate (8 mg/kg) and/or zinc chloride (2 mg/kg) daily for five consecutive days. Twenty-four hours after treatment, ALA-D activity was determined in the absence and presence of DL-dithiothreitol (DTT). The negative geotaxis behavior was assessed in 9- to 13-day-old rats. Treatment with lead and/or zinc did not affect body, brain or kidney weights or brain- or kidney-to-body weight ratios of the animals. In spite of the absence of effect of any treatment on ALA-D specific activity in brain, kidney and blood, the reactivation index with DTT was higher in the groups treated with lead or lead + zinc than in the control group, in brain, kidney and blood (mean + or - SEM; brain: 33.33 + or - 4.34, 38.90 + or - 8.24, 13.67 + or - 3.41; kidney: 33.50 + or - 2.97, 37.60 + or - 2.67, 15.80 + or - 2.66; blood: 63.95 + or - 3.73, 56.43 + or - 5.93, 31.07 + or - 4.61, respectively, N = 9-11). The negative geotaxis response behavior was not affected by lead and/or zinc treatment. The results indicate that lead and/or zinc treatment during the second stage of rapid postnatal brain growth affected ALA-D, but zinc was not sufficient to protect the enzyme from the effects of lead in brain, kidney and blood.

Effects of lead and/or zinc exposure during the second stage of rapid postnatal brain growth on delta-aminolevulinate dehydratase and negative geotaxis of suckling rats.

Lead has been shown to produce cognitive and motor deficits in young rats that could be mediated, at least in part, by inhibition of the zinc-containing heme biosynthetic enzyme delta-aminolevulinate dehydratase (ALA-D). In the present study we investigated the effects of lead and/or zinc treatment during the second stage of rapid postnatal brain development on brain, kidney and blood ALA-D specific activity, as well as the negative geotaxis behavior of rats. Eight-day-old Wistar rats were injected intraperitoneally with saline, lead acetate (8 mg/kg) and/or zinc chloride (2 mg/kg) daily for five consecutive days. Twenty-four hours after treatment, ALA-D activity was determined in the absence and presence of DL-dithiothreitol (DTT). The negative geotaxis behavior was assessed in 9- to 13-day-old rats. Treatment with lead and/or zinc did not affect body, brain or kidney weights or brain- or kidney-to-body weight ratios of the animals. In spite of the absence of effect of any treatment on ALA-D specific activity in brain, kidney and blood, the reactivation index with DTT was higher in the groups treated with lead or lead + zinc than in the control group, in brain, kidney and blood (mean +/- SEM; brain: 33.33 +/- 4.34, 38.90 +/- 8.24, 13.67 +/- 3.41; kidney: 33.50 +/- 2.97, 37.60 +/- 2.67, 15.80 +/- 2.66; blood: 63.95 +/- 3.73, 56.43 +/- 5.93, 31.07 +/- 4.61, respectively, N = 9-11). The negative geotaxis response behavior was not affected by lead and/or zinc treatment. The results indicate that lead and/or zinc treatment during the second stage of rapid postnatal brain growth affected ALA-D, but zinc was not sufficient to protect the enzyme from the effects of lead in brain, kidney and blood.