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L H Fossom

Publications and source records attributed to L H Fossom.

29 records · Page 2Linked to original sources
PubMed1990

Tyrosine hydroxylase mRNA in the dopaminergic neurons of young adult and aged mice by in situ hybridization.

Tyrosine hydroxylase (TH) mRNA in the dopaminergic neurons of the substantia nigra (SN) and the ventral tegmental area (VTA) in young adult and aged mice was detected and quantitated using in situ hybridization. Using 3H-labeled antisense RNA complementary to TH mRNA, these studies demonstrate the presence of TH mRNA in dopaminergic neurons of the SN and the VTA. Alternate sections stained immunocytochemically using TH-specific antiserum demonstrated that the neurons containing TH mRNA also contained TH protein. Quantitative analysis of the number of silver grains present over the dopaminergic neurons of the SN and VTA revealed no statistically significant difference between the two age groups. The results suggest that TH gene expression in dopaminergic neurons of the SN and VTA is not different in young adult and aged mice.

Aging↗
PubMed1987

Genetic correlation of ethanol-induced ataxia and cerebellar Purkinje neuron depression among inbred strains and selected lines of rats.

In the present study, we compared phenotypic differences in behavioral and neurophysiological responses to acute ethanol administration among six inbred rat strains. Genetic variation was found both for ataxia, as measured by loss of righting response (sleep time) after a hypnotic dose of ethanol, and for the depressant action of ethanol on the spontaneous discharge of cerebellar Purkinje neurons. Results from an analysis of covariance of these phenotypes, measured among the inbred strains, provided strong evidence for a high genetic correlation between sleep time and inhibition of cerebellar Purkinje neuron discharge in response to acute ethanol administration. However, ethanol metabolism was also found to correlate with the behavioral sensitivity of rats to ethanol. Preliminary data from the third generation of replicate lines of rats currently being selectively bred for high and low acute sensitivity to ethanol shows a trend toward divergence of both ethanol sleep time and neuronal sensitivity to acute ethanol. The conclusion from these data supports the hypothesis that the cerebellum is an important locus of ethanol action, and suggests that neuronal sensitivity to ethanol will continue to diverge between these rat lines as selection for the sleep time phenotype progresses.

Action Potentials↗
PubMed1985

Magnesium ion exerts a central role in the regulation of inhibitory adenosine receptors.

Guanine nucleotides and Mg2+ differentially regulate agonist binding to adenosine (Ri) receptors in fat-cell plasma membranes. GTP alone decreases binding of the agonist ligand [3H]N6-cyclohexyladenosine (CHA) by increasing the dissociation constant (Kd). Mg2+ alone also decreases [3H]CHA binding, which is associated with a decrease in the number of receptors and in the dissociation constant. In the presence of Mg2+, the effect of GTP is to increase [3H]CHA binding by increasing the total number of receptors. It thus appears that Mg2+ acts specifically at a bivalent-cation site which, with GTP, regulates agonist binding. This putative Mg site is highly sensitive to alkylating agents. Mild treatment with N-ethylmaleimide (NEM) abolishes the characteristic GTP effect on agonist binding in the presence of Mg2+. In addition, the effect of Mg2+ alone is also eliminated. The effect of GTP alone is largely unaltered. Studies of the adenylate cyclase activity indicate that this NEM treatment also abolishes the inhibition of basal activity by adenosine analogues, whereas guanylyl imidodiphosphate inhibition of forskolin-stimulated activity is only slightly impaired at this NEM concentration. These observations indicate that a Mg2+ 'site' or 'component' is required for the integration of receptor (Ri) occupancy with regulation of catalytic activity (C). The regulatory role of Mg2+ is more demonstrable in receptor-GTP-regulatory-protein (Ri-Ni) interactions than in GTP-regulatory-protein-catalytic-unit (Ni-C) interactions.

Adenosine↗
PubMed1985

Long lasting behavioral effects of dimethyl sulfoxide and the "peripheral" toxicant p-bromophenylacetylurea.

Behavioral toxic effects caused by a relatively small dose of the "peripheral" neurotoxin, p-bromophenylacetylurea (BPAU), and of its vehicle, dimethyl sulfoxide (DMSO) were investigated. BPAU induces, in rats, a central-peripheral distal axonopathy similar to that produced in humans by toxic organophosphorus-containing compounds, and has been proposed as a model to study this type of toxicity in a convenient experimental mammal. Rats were injected with BPAU (50 or 100 mg/kg) in DMSO (1 ml/kg), with DMSO alone, or with saline. 100 mg BPAU/kg produced permanent weight loss and hind limb paresis; the low dose did not. Behavioral testing, 2 days to 4 mo post-treatment, indicated that DMSO and/or 50 mg/kg of BPAU retarded habituation of spontaneous exploratory activity, impaired acquisition of conditioned (auto-shaped) behavior, and changed the dose-response relationship ford-amphetamine-induced suppression of operant (fixed ratio 32) responding. BPAU-treated animals were also impaired in initial performance of operant behavior maintained by a fixed ratio schedule of reinforcement, at high (greater than or equal to FR 16) ratio values. Thus, neurobehavioral toxicity may occur at doses too low to induce organophosphorus-type sensorimotor impairment or pathology. Further, DMSO may also exert effects on neurobehavioral function, suggesting it too may be potentially toxic within this domain.

Animals↗
PubMed1984

Amphetamine cumulation and tolerance development: concurrent and opposing phenomena.

Whether diminished or augmented behavioral effects are observed after repeated amphetamine administration may reflect the relative balance between tolerance and drug cumulation. To investigate this, we measured the distribution of d-amphetamine in various tissues and its effects on performance of a conditioned behavior after acute or chronic treatment. Rats trained to lever press under a fixed ratio 5 schedule for food-reinforcement were tested daily for 4 min epochs in each of 6 consecutive hours. After responding was stable, animals were injected for 16 days with saline or 1.0, 2.5 or 5.0 mg 3H-d-amphetamine sulfate/kg IP 15 min before the second daily behavioral epoch. On the 17th day, animals which had been receiving 3H-d-amphetamine were given their usual dose and those which had been receiving saline were given one of the doses of 3H-d-amphetamine; all animals were decapitated approximately 2 1/4 hours after this final injection, immediately after the 4th behavioral epoch. Brain, heart, muscle, epididymal fat, and kidney were removed for subsequent analysis of unchanged 3H-d-amphetamine. The experiment was carried out in two phases, 3 1/2 months apart, which inadvertently resulted in shipment of rats from different buildings on the supplier's campus. Acute treatment produced dose-related effects on operant responding, the lowest dose increasing responding and the highest dose suppressing it. Chronic injection of the highest dose of d-amphetamine resulted in significant attenuation of its acute suppressant effect. Additionally, chronic treatment suppressed responding of rats 23 1/4 hours after injection (i.e., before the subsequent daily injection). Tissue levels of d-amphetamine were dose related and d-amphetamine cumulated after chronic treatment with the highest dose. When d-amphetamine was administered acutely, the behavioural effect immediately before decapitation was highly correlated with the concentration of d-amphetamine in brain and in heart. This was not the case after chronic treatment, since rats given the higher doses showed less behavioural effect than would have been predicted from the concentrations of d-amphetamine in their tissues. Besides evidence of tolerance and cumulation of drug in one or more tissues, a significant phase or colony difference emerged, which could have been due to seasonal or other factors. Additional, different experiments, performed concurrently on a new shipment of rats from each colony, allowed us to conclude that the original observations of phase differences were not due to seasonal differences or chance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Metabolism of 3H-dopamine continuously perfused through push-pull cannulas in rats' brains: modification by amphetamine or prostaglandin F2 alpha.

Using perfusion cannulas implanted in the lateral cerebroventricles, the metabolism of a trace concentration of 3H-dopamine, continuously presented, was investigated in rats performing an operant for food reinforcement. The subjects were mature, drug-naive, male Long-Evans rats. Perfusate contained measurable quantities of 3H-3,4-dihydroxyphenylacetic acid (3H-DOPAC), 3H-3-methoxy-4-hydroxyphenylacetic acid (3H-homovanillic acid, 3H-HVA), 3H-3-methoxytyramine (3H-3-MT) and the 3H-noradrenaline metabolite, 3H-3-methoxy-4-hydroxyphenylethyleneglycol (3H-MHPG). Systemic injection of d-(1.5 mg/kg) or 1-(3.0 mg/kg) amphetamine resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate with a concurrent decrease in fixed-ratio 20 behavior. Addition of prostaglandin F2 alpha (10 ng/microliters perfused at a rate of 10 microliters/minute) had no effect on the rats' fixed-ratio 20 behavior or rectal temperature, but resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate. It is concluded that this methodology allowed us to monitor drug-induced changes in CNS dopaminergic and noradrenergic function in conscious rats engaged in schedule-controlled operant behavior. Furthermore, a trace concentration of PGF2 alpha in perfusion medium caused changes in 3H-dopamine metabolism in a manner similar to that of systemically administered amphetamines.

Amphetamine↗
PubMed1975

Postnatal elevation of brain tyrosine hydroxylase activity, without concurrent increases in steady-state catecholamine levels, resulting from dl-alpha-methylparatyrosine administration during embryonic development.

Increased specific activity of tyrosine hydroxylase (TH) in the brains of embryonic and 29-day-old chickens results from exposure to reserpine during the early stages of embryogenesis. We have also reported significant increases in the steady-state concentrations of catecholamines (CAs) in the brains of these 29-day-old chickens, suggesting permanent alterations in the control mechanisms during a critical period of development. The specificity of embryonic CA depletion in the above findings was examined usind dl-alpha-methyl-para-tyrosine (AMPT) as a depleting agent. AMPT, injected in varying doses into the yolk sac of fertilized chicken eggs prior to incubation, caused embryonic CA depletion by day 10 of embryogenesis but repletion had occurred by 20 days of embryogenesis. TH activity in whole brain and brain parts was elevated in a dose-related fashion at 29 days postnatally by AMPT. However, no changes in steady-state CA levels in whole brain were observed at this time after AMPT. Differences in the responses to reserpine and AMPT are discussed with respect to their pharmacological actions. The data support the contention that early embryonic CA depletion can result in long-term increases in TH activity postnatally, but steady-state levels of product need not necessarily be altered.

Age Factors↗