醋酸铅对雄性恒河猴生殖功能的影响

连续45d给予成年雄性恒河猴ig醋酸铅5和15mg·kg~(-1),结果血铅等铅接触指标发生明显改变;精子形态异常增多,活力下降;精液和睾丸铅含量,睾丸和附睾组织γ—GT和唾液酸的含量均显著增加,而SDH含量明显减少(P<0.05),丙二醛(MDA)和顶体蛋白水平改变无显著性意义,但表现出剂量-反应关系;睾丸超微结构可见,早期精子细胞顶体泡扩大,缺少顶体颗粒,支持细胞膜呈指状镶嵌,而精子数目变化无显著性意义;血清促滤泡素,促黄体素和睾酮水平无明显改变,提示下丘脑-垂体-性腺轴激素分泌机制和睾丸内精子发生过程尚无明显障碍,但成熟精子机能完善阻滞,受精力低下。     

铅对中枢神经系统功能及母体铅负荷对子代中枢神经系统发育的影响

采用猕猴作为实验对象进行了铅对中枢神经系统功能以及母体铅负荷对于代中枢神经系统发育的影响的实验研究。实验发现染铅组母猴脑铅和脑组织脂质过氧化物含量明显高于对照组（Ｐ＜０．０５），中枢神经递质５－ＨＴ含量降低。仔猴的观察指标改变与母猴相似。结果提示接触５～１５ｍｇ／ｋｇ剂量的醋酸铅可导致中枢神经细胞膜和功能的损害，并可发生中枢神经系统功能的改变。母体铅可经胎盘和乳汁传递至子代，长期铅接触可致子代脑发育不良。     

The effects of early lead exposure on auditory function in rhesus monkeys

Thirty-one female rhesus monkeys were randomly assigned to three lead exposure conditions (none, birth to 1 year, and birth to 2 years). Blood lead levels were maintained at 35–40 μg/dl beginning shortly after birth and continuing for 1 or 2 years postnatally. Auditory function was assessed in these monkeys at least 1 year after exposure to lead. The outcome measures included tympanometry to assess middle ear function, otoacoustic emissions (OAEs) to assess cochlear function, and auditory brainstem-evoked responses (ABRs) to assess the auditory nerve and brainstem pathways. There were no significant differences among the three experimental groups for any of the tympanometric variables measured suggesting no effect of lead exposure on middle ear function. Suprathreshold and threshold distortion product OAEs (DPOAEs) were comparable among the three groups. Finally, the auditory-evoked response at levels from the auditory nerve to the cerebral cortex did not significantly differ as a function of lead exposure. The lead exposure in this study had little effect on auditory function.     

Antiviral and side effects of interferons produced by recombinant DNA techniques as tested in rhesus monkeys

Human interferon type α₂ (HuIFN-α₂) produced by Escherichia coli was found to be as active as natural leukocyte interferon in protecting rhesus monkeys against intradermal vaccinia virus infection. HuIFN-β₁ produced in E. coli had similar but less pronounced activity. HuIFN-α₂ induced fever but not leukopenia, while HuIFN-β₁ had opposite effects. Concurrent treatment with acetosalicylic acid and prednisolone/azothioprine combinations did not interfere with the efficacy of the human interferons.     

重组人脑钠素对恒河猴长期毒性研究

目的:研究重组人脑钠素(rhBNP)对恒河猴的长期毒性.方法:健康恒河猴分别按体重随机分为低、中、高剂量组和空白对照组.低、中、高剂量组给药量分别为0.03,0.09和0.3mg·kg-1.连续30d静滴给药.末次给药后处死一半动物做病理解剖,另一半停药后继续观察15d.观察症状和检测指标包括:①血压、尿量等一般症状.②心电图.③红细胞、白细胞等血液学指标.④血钾、钠、氯、醛固酮等血液生化指标.⑤尿液检查.⑥抗体测定.⑦骨髓检查.⑧注射部位、心脏等病理检查.结果:动物连续给药后,高剂量组猴静滴后血压明显下降,中剂量组给药后血压有下降趋势但无明显差异.血压变化在3h内恢复正常.高、中剂量组给药后2h内尿量明显增加,但24h总尿量无明显改变.低剂量组血压及尿量无明显变化.d30病理组织学检查发现高剂量组少数动物出现肝细胞坏死,d45未发现有上述病理变化.肾组织也发现有病理变化,但存在于各个组,可能非药物所致.结论:rhBNP对猴心血管、泌尿系统有一定的药理毒理作用,主要表现为降血压、利尿,对肝脏可能有轻度毒性作用,其作用均是可逆的.rhBNP对恒河猴的安全剂量为0.03mg·kg-1.     

Chronic toxicity study with the serotonin antagonist amesergide administered nasogastrically to rhesus monkeys for one year

The chronic toxicity of amesergide, a selective (5HT₂/5HT_1c) serotonin antagonist, was evaluated in rhesus monkeys given daily nasogastric doses of 0, 5, 10, or 22.5 mg/kg for 1 year. An initial high dose of 25 mg/kg was reduced after approximately 1 week of dosing due to severe behavioral effects, including lethargy, a trance-like appearance, and rigidity, that interfered with the animal's ability to eat and drink. The behavioral effects, although still present at the new high dose of 22.5 mg/kg were less intense and subsided prior to subsequent daily dosing. All animals survived the treatment period. Clinical signs associated primarily with early treatment at the 25-mg/kg dose level resulted in reductions of body weights and food consumption. After the high dose was reduced from 25 mg/kg to 22.5 mg/kg, there were no significant effects on body weight gain or food consumption when compared to controls. Plasma concentrations of amesergide and its metabolites increased in a dose-dependent fashion. Areas under the plasma concentration-time curve (AUC) and peak plasma concentrations (Cmax) decreased substantially as the study progressed. Stress-related decreases occurred in leukocytic and erythrocytic parameters of high-dose males, but values returned to near pretest by study termination. Organ weights as well as gross and histological examination of tissues from animals of all treatment groups revealed no treatment-related lesions. No adverse effects occurred at daily doses of 5 or 10 mg/kg. © 1994 Wiley-Liss, Inc.     

Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure.

Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.     

The effects of benzamide analogues on cocaine self-administration in rhesus monkeys

Rationale: Based on the differential distribution of dopamine (DA) D₃ receptors in mesolimbic regions relative to nigrostriatal regions, the hypothesis was that D₃-selective antagonists (i.e., higher affinity at D₃- than D₂-receptors) would be more potent than D₂-selective antagonists at decreasing total cocaine intake relative to disrupting rates of responding. Objective: To evaluate the effects of acute administration of seven DA antagonists with varying affinities for D₂ and D₃ receptors in monkeys self-administering cocaine. Methods: Rhesus monkeys were trained to self-administer intravenous cocaine (0.01–0.3 mg/kg per injection) under a fixed-interval (FI) 5-min schedule during daily 4-h sessions. The use of a FI schedule allowed for independent assessment of rate effects and changes in reinforcement frequency as a consequence of drug pretreatments. The compounds examined, in order of D₃ binding affinity, were: 2,3-dimethoxy-N-(9-p-fluorobenzyl)-azabicyclo[3.3.1]nonan-3β-yl benzamide (MABN) = eticlopride = 5-bromo- 2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl]benz-amide (BBP) > spiperone > fluoroclebopride (FCP) > 2,3-dimethoxy-N-(p-fluorobenzyl)piperdin-4-yl benzamide (MBP) > haloperidol. Results: In the absence of any pretreatments, cocaine-maintained responding varied as a function of dose and was characterized as an inverted U-shaped function, while cocaine intake increased in a dose-related fashion. When the dose of cocaine that maintained peak rates was available, all DA antagonists decreased response rates and cocaine intake in a dose- dependent manner. Increases in cocaine dose attenuated the effects of the DA antagonists, resulting in rightward shifts of the cocaine dose–response curves. Based on the ratio of behavioral potency at decreasing response rates relative to intake (ED₅₀ rate/ED₅₀ intake) when the highest cocaine dose was available, the order of potency and ED₅₀ ratio values were: MABN (2.5) > eticlopride (1.63) > BBP = spiperone (1.5) > FCP (1.35) > MBP = haloperidol (0.89). This order parallels each compound’s affinity at D₃ receptors (r ²=0.84) to a greater degree than D₂ receptor affinity (r ²=0.34). Conclusions: These results, using a FI schedule of cocaine self-administration, suggest that D₃ receptor antagonists are more likely to selectively decrease intake relative to response rates than D₂ receptor antagonists. Received: 8 January 1999 / Final version: 15 June 1999     

Skeletal effects of developmental lead exposure in rats.

To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.     

The effects of dopaminergic agents on reaction time in rhesus monkeys

 Many CNS pathologies, including Parkinson’s, Alzheimer’s and Huntington’s diseases, as well as AIDS dementia complex, involve some degree of movement dysfunction. Reaction time (RT) performance has been shown to be a sensitive measure of motor function for these disorders. Useful models of RT performance exist in a variety of species, but few are performed in the same manner as with humans. To facilitate species comparisons, the present RT task was developed from a human RT task. Dopaminergic drugs were then used to characterize the sensitivity of the model to CNS changes and to investigate their effects on RT performance in intact rhesus monkeys. With cumulative dosing, the selective dopamine receptor antagonists (D₁) SCH 39166 and (D₂) raclopride produced dose-dependent slowing of RT performance. Results following bolus administration of these drugs were consistent with the cumulative dosing procedure, although of smaller magnitude and higher variability. Amphetamine had no significant effect on group RT performance with either dosing scheme, but RT performance in individual monkeys was either speeded or slowed by d-amphetamine. The present results suggest that blockade of either D₁-like or D₂-like dopamine receptors can slow RT performance in rhesus monkeys and that this paradigm may be useful to study movement dysfunction in non-human primates. Received: 19 May 1997 / Final version: 14 November 1997     

The effects of behavioral history on cocaine self-administration by rhesus monkeys

The purpose of the present study was to examine whether a history of responding under schedules that generate either high or low response rates could modify previously established cocaine self-administration. Eight experimentally naive rhesus monkeys were trained to respond on one of two levers under a fixed-interval (FI) 5-min schedule of intravenous cocaine (0.03 mg/kg per injection) presentation. When responding was stable a cocaine dose-response curve (saline, 0.01–0.3 mg/kg per injection) was determined. Following completion of the dose-response curves, the monkeys were randomly assigned to one of two groups (n=4/group) and trained to respond on the other lever under either a fixed-ratio (FR) 50 or inter-response times (IRT) > 30-s schedule of cocaine (0.03 mg/kg per injection) presentation. After 65 sessions responding was again maintained under the FI5-min schedule of 0.03 mg/kg per injection cocaine for 60 sessions, followed by redetermination of the cocaine dose-response curve. During the initial exposure to the FI schedule, the mean rate of responding was 4.02 (± 0.33) responses/min and the cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. The FR50 schedule generated high rates (66.80 ± 5.6 responses/min), while response rates under the IRT > 30-s schedule were low (2.62 ± 0.2 responses/min). Following different behavioral histories, response rates under the FI5-min schedule were significantly higher for 60 sessions in FR-history monkeys compared to IRT-history subjects. Compared to the initial FI baselines, cocaine intake (mg/kg per session) was significantly higher following an FR-history and significantly lower following training under an IRT schedule, for 60 consecutive sessions. In addition, there was a significant effect of behavioral history on the cocaine dose-response curve, such that descending limb was shifted farther to the right in FR-history subjects compared to IRT-history monkeys. Results from the present study indicate that previously established drug-seeking behavior can be modified by training under different reinforcement schedules. Knowledge of such historical variables may be important in understanding the determinants of drug self-administration.     

The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys

BACKGROUND

Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer''s disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11–17 years old) and aged (20–31 years old) rhesus macaques.

EXPERIMENTAL APPROACH

The effects of dimebolin (3.9–118 µg kg⁻¹) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 µg kg⁻¹) of scopolamine.

KEY RESULTS

In both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals.

CONCLUSIONS AND IMPLICATIONS

Here we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.     

The effects of succimer chelation therapy on auditory function in rhesus monkeys

Sixty-six female rhesus monkeys were randomly assigned to three lead exposure conditions (none, from birth to 1 year, and from birth to 2 years) by two chelation treatment (succimer and no succimer) conditions. Blood lead levels were maintained at 35–40 μg/dl beginning shortly after birth and continuing for 1 or 2 years postnatally. There were two separate chelation regimes: 53 and 65 weeks of age. Lead and lead–vehicle dosing were discontinued while succimer was administered. Succimer (or placebo) was administered orally at a dose of 30 mg/kg/day (divided into three doses per day) for 5 days and for 14 additional days at 20 mg/kg/day (divided into two doses per day) for a total 19-day treatment regimen. Auditory function was assessed in these monkeys at least 1 year after lead intake had been discontinued. The outcome measures included tympanometry to assess middle ear function, OAEs to assess cochlear function, and ABRs to assess the auditory nerve and brainstem pathways. There were no significant differences as a function of succimer treatment for any of the tympanometric variables measured. Suprathreshold and threshold distortion product otoacoustic emissions were comparable among the succimer and vehicle groups. However, there was a nonsignificant trend to smaller amplitude distortion products at the highest frequencies assessed (6.4–10.0 kHz). Finally, the auditory evoked response at levels from the auditory nerve to the cerebral cortex did not significantly differ as a function of succimer treatment.     

Young brains on lead: adult neurological consequences?

Gilbert and colleagues examine the effect of chronic low-levellead exposure, occurring during development, on hippocampalneurogenesis and spatial learning in adulthood. The effectsof lead exposure on cognitive and behavioral deficits in childrenleading to learning and memory impairments is well established,whereas there is little information on the long-term (adult)consequences of gestationally initiated lead exposure. One importantissue that Gilbert and colleagues assess is the long-term consequencesof chronic developmental low-level lead exposure in adult offspring.Secondly, Gilbert and colleagues are the first to report theeffect of lead exposure on hippocampal neurogenesis. The work by Gilbert and colleagues is intriguing, in view ofthe fact that this paper attempts to integrate the consequencesof developmental exposure to lead, known for its ability toimpair cognitive functions, such as learning and memory, witha dysfunction in adult hippocampal neurogenesis. Chronic leadexposure initiated during development     

Psychophysiologic effects of early lead exposure.

In several separate experiments neonatal rats were intubated daily with 9, 27 or 81 mg lead acetate/kg of body weight throughout their 3-week postnatal period of development. Based on average body weights, the total daily lead intake was 0.156, 0.454 or 1.384 mg lead per animal, respectively (in addition to normal lead intake from the environment). Subtle and specific behavioral changes, involving an inability to attenuate inappropriate behavior in a two-way shuttle or a habit-reversal operant task, occurred in offspring following exposure to a minimum of 0.454 mg lead per day. The specificity of this central dysfunction was such that motor activity was normal, stress responsiveness remained unaffected and simple learning ability was comparable to that of controls. The only indication of a central neurochemical modification accompanying this behavioral defect was a tendency for telencephalic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities to be depressed, suggesting a possible involvement of the cholinergic system. Steady-state levels of brain monoamines were unaltered. The experimental weanlings displayed an inhibition of blood delta-amino levulinic acid dehydratase (ALAD) activity, a parallel reduction in regional brain ALAD activity, a moderate reduction in hematocrit and hemoglobin and an increase in kidney weight. This latter effect occurred even at the lowest level of lead intake, 0.156 mg lead per day.     

Age of testing as a factor in the behavioral effects of early lead exposure in rats

The behavioral effects of postnatal administration of lead during weaning were tested in young and adult rats. Rats received either 10 mg/kg IP lead acetate or equimolar sodium acetate daily for the first twenty days of life. Tests of performance on an 8-arm radial maze and a passive avoidance task were begun at 25 days after birth or 90 days after birth. Lead-treated rats did not perform significantly different than control rats on the radial arm maze at either age tested. Young lead-treated rats performed with significantly longer lick latencies than young control rats on the passive avoidance task. Adult lead-treated rats performed with shorter food latencies than adult control rats. A group of young rats was retested on the passive avoidance task at 150 days after birth. Performance on the retest was similar to their early performance. Differences in performance of young and adult lead-treated animals on the passive avoidance task are discussed in terms of an interaction of the effects of lead exposure, maturation, and early experience.     

GM-CSF／IL-3融合蛋白对环磷酰胺引起的猕猴骨髓造血功能抑制的影响

目的观察粒细胞-巨噬细胞集落刺激因子（GM—CSF）／白细胞介素3（IL-3）融合蛋白对环磷酰胺（L-TX）引起的造血系统抑制的缓解作用。方法连续2d静脉注射CTX50mg·kg^-1·d^-1后将21只猕猴分为4组,其中3组分别皮下注射GM—CSF／IL-3融合蛋白20、40、80μg·kg^-1·d^-1,连续16d,剩余一组为溶剂对照组。停药后10d抽取猕猴骨髓,做骨髓涂片检查及进行骨髓祖细胞半固体培养。结果GM—CSF／IL-3融合蛋白各剂量组明显促进CTX应用后猕猴骨髓有核细胞增生。GM-CSF／IL-3融合蛋白低、中剂量促进猕猴骨髓粒-巨噬系（CFU—GM）、红系（早期BFU-E、晚期CFU—E）及巨核系（CFU-MK）祖细胞的增殖;高剂量对三系祖细胞的增殖无促进作用。结论GM—CSF／IL-3融合蛋白促进CTX所致猕猴造血功能抑制的恢复。     

Differential effects of early chronic lead exposure on postnatal rat brain NMDA,PCP, and adenosine A1 receptors: An autoradiographic study

The deleterious effects of postnatal lead (Pb) exposure on neural development, synaptic plasticity, and cognitive function have been well documented in laboratory animals. While the exact mechanisms by which Pb produces long-lasting neurotoxicity remain unknown, recent evidence suggests that Pb may interact with and/or disrupt the N-methyl-D-aspartate/phencyclidine receptor complex and the associated ion channel. In addition to perturbations of excitatory amino acid neurotransmission, chronic Pb exposure may also have deleterious effects on inhibitory mechanisms such as that provided by purinergic neuromodulation. In order to further examine the possibility that alterations of both excitatory and inhibitory neurotransmission may contribute to the neurotoxic actions of Pb, the effects of early Pb exposure on ligand binding to postnatal rat brain N-methyl-D-aspartate (NMDA), phencyclidine (PCP), and adenosine A₁ receptors were examined using quantitative autoradiography techniques. Rat pups nursed mothers exposed to 4% PbCO₃ in their diet or a Na₂CO₃ control diet from postnatal day 1 (P1) to P25. At P25, rats were sacrificed and the regional distributions of brain NMDA, PCP, and adenosine A₁ receptors were examined. Chronic lead exposure was found to produce a specific increase in [³H]CGP 39653 binding to NMDA receptors in the hippocampus. [³H]1-(1-[2-thienyl)cyclohexyl]-piperdine ([³H]TCP) binding to PCP receptors was largely unaffected by the chronic Pb treatment. In contrast, [³H]cyclohexyladenosine ([³H]CHA) binding to adenosine A₁ receptors was markedly reduced in many brain regions with the largest decreases observed in the cerebellum. These results indicate that neonatal Pb exposure produces a specific alteration of both excitatory and inhibitory neuromodulatory mechanisms in the postnatal rat forebrain that may underlie the behavioral hyperactivity and increased seizure sensitivity associated with Pb neurotoxicity. © 1993 Wiley-Liss, Inc.     

A meta-analysis of studies investigating the effects of lead exposure on nerve conduction

Group means from nerve conduction studies of persons exposed to lead were used in a meta-analysis. Differences between the control and exposed groups, and the slopes between nerve conduction measurements and log(10) blood lead concentrations were estimated using mixed models. Conduction velocity was reduced in the median, ulnar, and radial nerves in the arm, and in the deep peroneal nerve in the leg. Distal latencies of the median, ulnar, and deep peroneal nerves were longer. No changes in the amplitudes of compound muscle or nerve action potentials were detected. The lowest concentration at which a relationship with blood lead could be detected was 33.0 microg/dl for the nerve conduction velocity of the median sensory nerve. Lead may reduce nerve conduction velocity by acting directly on peripheral nerves or by acting indirectly, for example, on the kidney or liver.     

The effects of developmental and/or direct lead exposure on FR behavior in the rat

In the present study, 21-day old female rats were exposed to daily doses of 750 mg/kg of lead acetate via a restricted water intake regimen for 70–80 days prior to mating. Treatment was then continued throughout gestation and nursing. At weaning, litters from half of the treated and control mothers were placed on treatment for the remainder of the experiment. This manipulation yielded four groups for testing: Group Pb/Pb, developmental and direct, postweaning exposure; Group Pb/C, developmental exposure only; Group C/Pb, direct exposure only; and Group C/C, no exposure to lead acetate treatment. Beginning at 42–49 days of age, offspring were shaped to bar press on a Fixed Ratio 20 (FR20) schedule of reinforcement and then received 20 sessions each 20 min in length. Analyses revealed that Group Pb/Pb received significantly fewer reinforcements/min across sessions than the other three groups and also took significantly longer to emit each 20 response block. Contrary to previous reports in the literature, it is suggested that rats may not be impervious to postweaning lead exposure, particularly when there is a history of developmental exposure.