Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats.

Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR.

Behavioral and biochemical assessment of time-related changes in globus pallidus and striatal dopamine induced by intranigrally administered neurotensin.

Microinjection of neurotensin (NT; 2 and 5 micrograms) into the substantia nigra zona compacta caused an increase in dopamine (DA) and DA metabolites in the rodent globus pallidus and striatum which persisted for at least 20 hours after peptide administration. Similar NT treatments given unilaterally into the nigra caused circling away from the injected side in amphetamine-pretreated rats, but were without effect when microinjected into saline-pretreated animals. Circling also occurred when the animals were given amphetamine 20 hours after intranigral NT administration. Contralateral rotation was observed with unilateral intranigral injections of gamma-hydroxybutyric acid (GHB; 400 micrograms) or with lower intranigral GHB doses (250 micrograms) in amphetamine-pretreated animals. The effects of GHB and NT differed in the manner in which the animals rotated as well as in the profile of DA and DA metabolite changes induced by these drugs. These studies indicated that: dopaminergic functions of the globus pallidus are influenced, like the striatum, by manipulations of the substantia nigra: NT and GHB likely act via different mechanisms to effect nigral dopamine-containing cells; and NT was capable of inducing changes in dopamine neurons which had long term consequences.

The intra-axonal transport of polypeptide H: evidence for a fifth (very slow) group of transported proteins in the retinal ganglion cells of the rabbit.

We have determined that a genetically polymorphic polypeptide (H, molecular weight approximately equal to 195,000) of the rabbit nervous system is transported down the retinal ganglion cell axons at a velocity of 0.7-1.1 mm/day. The H-polypeptide and probably at least two additional polypeptides (molecular weights approximately 145,000 and 73,000) therefore compose a group of intra-axonally transported proteins which moves more slowly than the 4 groups previously described in these neurons. The polypeptides of this fifth group are similar in molecular weight to certain polypeptides transported slowly in other mammalian neurons.

A methodology for speciation of methyltins in mammalian tissues.

Exposure to methyltin compounds results in morphologically detectable damage to several mammalian organ systems. Although reliable dose-response relationships have been described, a fast method for quantitating levels of various methyltin species in target organs has been unavailable. It has been possible to measure organotins as total tin using atomic absorption spectrometry, but speciation of methyltins has proved difficult. We present a rapid method for quantitative analysis and speciation of methyltins, direct from mammalian tissues. Methyltin compounds (monomethyltin trichloride, dimethyltin dichloride, trimethyltin chloride, and tetramethyltin) are purged from freshly homogenized mouse kidney and brain tissues using NaBH4. The volatile organotin hydrides produced are cryogenically trapped on the head of a gas chromatographic column (at -40 degrees C) and eluted using a linear temperature program (15 degrees C/min to 190 degrees C). The compounds are detected using selected ion monitoring in a Hewlett Packard 5985-B mass spectrometer. Quantitation is achieved by integration of the areas of the chromatographic peaks. Linear response is obtained over the range of 1 ng to 30 micrograms for each compound. Recoveries of methyltins spiked into tissues are greater than 85%.

Neurotoxicants: emerging issues and policy options.

Neurotoxicants are increasingly seen as significant public health hazards, the resolution of which is influenced by science as well as economics, politics, and emotions. Three topical issues are presented to illustrate the application or abuse of scientific data in the political arena and to suggest appropriate responsibilities of scientists beyond the generation of data. The examples include regulation of occupation-related neurotoxic exposure, transfer of neurotoxic pollutants among environmental media, and export of neurotoxic hazards to Third World countries. These examples illustrate the variety of ways in which neurotoxicants impinge on policy questions--from international trade, through ecosystem effects, to personal occupational health and safety.

Haematology and pathology of captive southern grasshopper mice (Onychomys torridus).

A colony of Onychomys torridus was evaluated for the prevalence of infectious, parasitic and congenital diseases. Multiple limb defects including brachydactyly, syndactyly, and hemimelia were observed in offspring from the colony. The colony was parasitized by Ornithonyssus bacoti (tropical rat mites) on 2 occasions. No infectious diseases were detected. Normal haematologic values were determined in healthy adult animals.

Health risk assessment practices in the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration (FDA) regulates a wide variety of consumer products. Safety issues involve chemical and microbial contaminants in food, biologies, and medical devices; side effects from prescription and nonprescription drugs; residues of animal drugs in food; and radiation from electronic devices. Because of this wide diversity, the legal standards, rules, and policies governing the regulation of these products differ considerably. Hence, risk assessment and risk management practices within the FDA are of necessity quite diverse. This paper presents a summary of risk assessment practices at each of the product centers of the FDA (Center for Food Safety and Applied Nutrition, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Center for Veterinary Medicine) and of the development of risk assessment procedures at the National Center for Toxicological Research.