triethyllead and Brain-Diseases

Topics: Animals; Brain; Brain Diseases; Embryonic and Fetal Development; Humans; Intellectual Disability; Methylmercury Compounds; Organometallic Compounds; Rats; Trimethyltin Compounds

Acute exposure to triethyl lead chloride (7.88 mg/kg) enhanced the behavioral effects of both direct- and indirect-acting dopaminergic agonists. Rats treated with lead 1 week before testing exhibited an increased response to the motor stimulant effects of D-amphetamine and apomorphine. The dose-response curves for D-amphetamine (1.25, 2.0, 3.15 and 5.0 mg/kg)- and apomorphine (0.2, 0.5, 1.25 and 2.0 mg/kg)-induced hyperactivity were shifted to the left in the triethyl lead group. Finally, apomorphine (1 mg/kg) produced more stereotypy in rats pretreated with triethyl lead. This enhanced sensitivity to dopaminergic agonists was not due to altered pharmacokinetics of the challenge drugs, since the onset and duration of their behavioral effects were not affected by triethyl lead. Furthermore, the regional distribution and accumulation of D-[3H]amphetamine was not altered by triethyl lead. These data suggest that acute exposure to triethyl lead enhances the responsiveness of dopaminergic processes which contribute to locomotor activity. The involvement of brain dopamine in other aspects of organolead neurotoxicity is discussed.

Topics: Animals; Apomorphine; Brain Diseases; Dextroamphetamine; Dopamine; Drug Interactions; Lead; Male; Motor Activity; Organometallic Compounds; Rats; Rats, Inbred F344; Stereotyped Behavior

Alkyl leads (R x Pb) are environmentally prevalent compounds which have been shown to produce a variety of neurological and behavioral deficits in both laboratory animals and man. Due to the increasing commercial use of these compounds, the episodes of human poisoning, and the limited understanding of their sites and mechanisms of toxicity, the organoleads, as a class, remain potentially important environmental health hazards. Recent data indicate that the constellation of behavioral effects produced by these compounds resembles the behavioral sequelae of limbic system damage. For example, alterations in sensory responsiveness and/or behavioral reactivity and task-dependent changes in avoidance learning are observed following organolead exposure and experimental disruption of the limbic system. Furthermore, neurochemical changes induced by organoleads are regionally-specific and restricted to the limbic forebrain and frontal cortex. The present review will summarize the toxic properties of organoleads, discuss their neurobehavioral effects, and suggest that these effects might be attributable to a disruption of the limbic forebrain.

Topics: Animals; Behavior, Animal; Brain Diseases; Chemical Phenomena; Chemistry; Disease Models, Animal; Humans; Kinetics; Lead; Lead Poisoning; Limbic System; Organometallic Compounds; Rats; Tetraethyl Lead

The immature brain is unduly vulnerable to the toxic effects of triethyllead (Et3Pb). Both brain growth and main developmental events in the tissue are appreciably restrained by this neurotoxin. Generally, the susceptibility of brain cells to Et3Pb appears to diminish with age. The major cellular alterations in the affected tissue include the destruction of cell processes, and swelling and vacuolization in the pericaryon. The effect of Et3Pb-induced poisoning is one of hypomyelination as seen from the prominent reduction in the content of cerebral myelin. Myelin-producing cells (oligodendrocytes) seem to be particularly vulnerable to Et3Pb relative to other components of the tissue. Furthermore, the toxin specifically hampers the process of myelin membrane assembly. The inhibitory effects of Et3Pb can be attributed to the interaction of this amphiphilic compound with cellular membranes and with the process of their biogenesis.

Topics: Animals; Brain; Brain Diseases; Cells, Cultured; Chick Embryo; Disease Models, Animal; Energy Metabolism; Lead; Myelin Sheath; Nerve Tissue Proteins; Organometallic Compounds; Rats