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J F Ross

Publications and source records attributed to J F Ross.

53 records · Page 3Linked to original sources
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Disinhibitory effects of intrahippocampal of intrahypothalamic injections of anticholinergic compounds in the rat.

The effects of intrahippocampal or intrahypothalamic injections of anticholinergic compounds on operant responding were observed in a multiple schedule paradigm consisting of reinforced, punished, and nonreinforced components and on a punished ingestive passive avoidance task. The pattern of results suggests that cholinergic components of the hippocampus and hypothalamus mediate responding suppressed by nonreinforcement but not by punishment. The data are discussed with reference to Carlton's proposed central cholinergic inhibitory mechanisms.

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ZPT-related distal axonopathy: behavioral and electrophysiologic correlates in rats.

These experiments examined the relationship between behavioral and electrophysiologic signs of neuromuscular dysfunction in rats with zinc pyridinethione (ZPT)-induced neurotoxicity. ZPT added to the diet of adult rats at 50 ppm produced a moderate (approximately 200 g) reduction in forelimb and hindlimb grip strength which occurred during the second week of dosing. Other behavioral tests of peripheral nervous system toxicity were affected inconsistently. Electrophysiologic changes included a marked (maximum 95%) reduction of indirect muscle-evoked potential (M-wave) and a decrement (maximum 30%) during repetitive M-wave elicitation. Electrophysiologic changes were greater in hindlimb than in forelimb. Needle electromyography revealed denervation potentials in ZPT-treated rats which appeared after M-wave changes and recovered faster than did M-wave amplitude. Caudal nerve conduction velocity was unaffected, indicating that peripheral neurotoxic effects were confined to the neuromuscular junction. When ZPT exposure was discontinued, grip strength recovered in about 1 week. In contrast, electrophysiologic measures required 42 days to recover completely. These results indicate that deficits in neuromuscular junction physiology are a sensitive index of ZPT-related distal axonopathy.

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Quantification of the hindlimb extensor thrust response in rats.

This report describes a procedure for measuring the extensor thrust response (ETR) and summarizes the results of initial validation experiments using adult Long-Evans rats. The ETR can be quickly elicited and the force measured by pressing against the hindlimb footpads with a small rectangular plate or bar attached to a digital force gauge. Output of the force gauge is analyzed and displayed with commercially available hardware and software. The first experiment compared the acute effects of i.p. injection of chlorpromazine (CPZ; 1, 4, or 7 mg/kg) or amphetamine (AMP; 0.3, 1, or 3 mg/kg) on the ETR and forelimb/hindlimb grip strength (FL/HL-GS) in male and female rats. CPZ decreased both ETR and FL/HL-GS values. Both 1 and 3 mg/kg AMP increased grip strength values but decreased ETR values. A second experiment compared the evolution of changes in ETR, FL/HL-GS, and peripheral neurophysiological measures during 8 weeks of daily oral dosing of 10 mg/kg acrylamide (ACR) monomer. ACR-treated rats exhibited a progressive decrease in ETR beginning after 3 weeks of dosing, whereas a reduction of HL-GS was observed beginning much later, after 7 weeks of dosing. The deficit in ETR progressed in the absence of any changes in spontaneous or evoked electrophysiological abnormalities in neuromuscular function, but was accompanied by a decrease in peripheral nerve conduction velocity. Taken together, the results indicate that the ETR can be used to characterize functional effects in both single dose and repeated dose experiments. The data also indicate that the ETR does not merely duplicate the information provided by FL/HL-GS, and suggest a hypothesis that the ETR may be sensitive to neurotoxicant-induced changes in somatosensory function.

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Integrated evaluation of central nervous system lesions: stains for neurons, astrocytes, and microglia reveal the spatial and temporal features of MK-801-induced neuronal necrosis in the rat cerebral cortex.

Routinely processed, hematoxylin and eosin (H&E)-stained slides are typically used to assess the morphologic integrity of the central nervous system in neurotoxicity safety studies. However, the value of special stains for improving neuropathologic evaluations during the assessment of neurotoxicity has been emphasized in the neuroscience literature and by regulatory agencies. The primary objective of the present study was to characterize the spatial and temporal changes in neurons, astrocytes, and microglia after dizocilpine maleate (MK-801)-induced focal neuronal necrosis in the posterior cingulate/retrosplenial (PC/RS) cortex of the rat. A secondary objective was to evaluate the application of special stains and a novel sectioning procedure for detecting neurotoxicity. Sixty adult male Sprague-Dawley rats were treated with sterile water vehicle or 10 mg/kg MK-801 and perfused through the left ventricle (pumped at 65 mm Hg pressure) with 10% neutral buffered formalin or 4% paraformaldehyde at 4 hr and on days 1, 3, 7, 14, and 28 after treatment. For light microscopic evaluation, brain sections were stained with H&E, a special cupric-silver (CS) stain that selectively impregnates degenerating neurons and makes them readily evident, glial fibrillary acidic protein (GFAP) immunohistochemistry for astrocytes, and Griffonia simplicifolia isolectin B4(GSA) histochemistry for microglia. Brains perfusion-fixed with 4% paraformaldehyde were prepared for CS staining with a novel frozen-sectioning procedure for multiple embedding in a composite gelatin block. In H&E sections from treated rats, necrotic nerve cell bodies were observed in PC/RS cortical layers 3 and 4 on days 1, 3, 7, and 14, but not on day 28. These necrotic neurons required high magnification for detection (x20 objective, x10 ocular). In contrast, degenerating neurons selectively stained with CS were observed in the same location as necrotic neurons seen with H&E but at low magnification (x2 objective, x10 ocular). Cupric-silver staining showed details not seen with H&E, including dendritic and axonal degeneration with progressive fragmentation. Beginning on day 3, GFAP immunohistochemistry revealed hypertrophic astrocytes in a diffuse pattern throughout the region of cell body necrosis, a change that persisted throughout the study. However, GSA lectin histochemistry identified a few reactive microglia on day 1 in a multifocal pattern throughout the region of cell body necrosis. Reactive microglia were observed on days 3, 7, and 14, but not on day 28. Glial changes observed with H&E staining were limited to an increase in the cellularity of glial cell nuclei in the area of neuronal necrosis. This study provides a comprehensive and integrated view of the temporal changes occurring in neurons, astrocytes, and microglia during acute neurotoxic injury. Moreover, advantages for using new staining and sectioning methodologies to enhance the toxicologic evaluation of the central nervous system are demonstrated.

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