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The purpose of the present study was to determine whether exposure to amphetamine during the preweanling period would impact the learning or reward processes of rats tested in adulthood. In three experiments we examined whether amphetamine treatment (0-10 mg/kg per day) on postnatal days 11-17 altered the subsequent performance of adult Sprague-Dawley rats on a step-down passive avoidance, active avoidance, or novelty-seeking task. There was no evidence that postnatal amphetamine exposure affected performance on any of these tasks. These results suggest that the long-term impact of pre- and postnatal psychostimulant exposure differs, because in utero stimulant treatment is known to produce learning deficits and decrease reinforcement efficacy of rats tested in adulthood.

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The dose-response relationship between aerosolized leukotriene B4 (LTB4 and pulmonary neutrohilia was examined in a group of five rhesus monkeys. The effects of an oral dose of LY293111Na on LTB4-aerosol-induced pulmonary neutrophilia were also examined. Ex vivo expression of CD11b receptors on polymorphonuclear leukocytes from bronchoalveolar lavage fluid and peripheral whole blood were also assessed. Up-regulation of CD11b adhesion receptors by LTB4 was assessed ex vivo on the peripheral whole blood. Pulmonary neutrophilia was linearly associated with dose of inhaled LTB4. LY293111Na, at 10 mg/kg, significantly blocked the profound bronchoalveolar lavage neutrophilia produced by LTB4 aerosol inhalation. A large (48%), but not statistically significant, reduction was seen for CD11b expression on bronchoalveolar lavage polymorphonuclear leukocytes after pretreatment with LY293111Na. LY293111Na did not significantly change the number of white blood cells in peripheral blood. LY293111Na did significantly attenuate the LTB4-induced up-regulation of CD11b receptors on peripheral blood neutrophils. We conclude that LY293111Na may be an effective oral treatment for diseases that involve neutrophilic inflammation.

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An automated reticulocyte counting method that used a flow cytometer and the nucleic acid staining dye, thiazole orange, was developed. Anticoagulated (EDTA) blood specimens were suitable for flow cytometric reticulocyte counting when stored at 4 C for 96 hours after collection. Thiazole orange-stained samples were stable for 5.5 hours after staining when stored capped at 20 C and protected from light. Flow cytometric and manual microscopic reticulocyte counts were compared for counts in the 0.27 to 5.32% range (as determined by flow cytometry) and 0.10 to 4.90% range (as determined by 1 technician). Although the results of flow cytometric analysis generally correlated well (r = 0.821) with manual counts, there was poor correlation between the procedures for counts less than or equal to 2.0% (r less than or equal to 0.272). Linearity of flow cytometric counts over the range 0.27 to 14.46% was excellent (r = 0.999). Within-run precision of flow cytometric counts (% coefficient of variation [cv] = 3 to 5) was superior to manual microscopic counts obtained by one technician (% cv = 19 to 23) and to manual microscopic counts, which were an average of counts done by 3 technicians (% cv = 8 to 18). Comparable flow cytometric counts were obtained by counting 50,000 or 100,000 blood cells in the flow cytometer.

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N-Methyltetrazolethiol (NMTT) and NMTT-containing cephalosporin antibiotics cause characteristic testicular lesions in young but not adult rats. In addition, NMTT-containing cephalosporins inhibit aldehyde dehydrogenase and have been associated with a disulfiram-like reaction in humans and animals. Therefore, the potential testicular toxicity of disulfiram (10, 30, or 100 mg/kg) was evaluated in 37-day-old rats given oral doses on Postpartum Days 6 through 36, and was compared to the toxicity induced by NMTT (100 mg/kg). NMTT and each dose of disulfiram caused a decrease in testes weight. By DNA flow cytometry, testicular cell suspensions from rats given 100 mg/kg of NMTT had a 40% reduction in spermatids while those from rats given 10, 30, or 100 mg/kg of disulfiram had reductions of 52, 61, or 89%, respectively. Microscopically, the testes of rats given either NMTT or disulfiram had qualitatively similar changes, characterized by delayed maturity of the leading waves of germinal cells which had reached early maturation phase in control animals. Moderate to severe reduction occurred in the total number of spermatids with complete absence of acrosome phase and maturation phase spermatids. There was also a prominent reduction in the number of spermatocytes. Reduction in number of spermatogonia was minimal. While the mechanism of toxicity is not known for either compound, it is possible that the toxicity was related to the enzyme-inhibitory effects which both compounds possess. By defining the mechanism of testicular toxicity for compounds which cause a NMTT-like testicular toxicity in rats, biological differences in the spermatogenic process between the young and adult rat may be further understood. Direct extrapolation of the testicular effects in neonatal rats to man is not possible because of the substantial differences in initiation of spermatogenesis between rodents and humans.

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