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Biomedical subjects

R W Fuller

Publications and source records attributed to R W Fuller.

At least 343 records · Page 19Linked to original sources
PubMed1982

Dopamine deficiency in the weaver mutant mouse.

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.

Animals↗
PubMed1982

Effects of L-dopa on epinephrine concentration in rat brain: possible role of inhibition of norepinephrine N-methyltransferase by S-adenosylhomocysteine.

L-Dopa injected at 200 mg/kg i.p. into rats caused a slight reduction in hypothalamic concentration of epinephrine and completely prevented the accumulation of epinephrine after monoamine oxidase inhibition. The lowering of epinephrine concentration was greater with L-dopa than with D-dopa, was dose-related over a dosage range of 50 to 200 mg/kg of L-dopa and was not prevented by a dopamine receptor antagonist. Hypothalamic norepinephrine N-methyltransferase activity measured in vitro was not altered in rats treated with L-dopa. L-Dopa injection decreased S-adenosylmethionine (SAMe) concentration and increased S-adenosylhomocysteine (SAH) concentration in hypothalamus, probably a result of extensive O-methylation of L-dopa and its metabolites. The decrease in SAMe and epinephrine concentration and the increase in SAH concentration occurred at lower doses of L-dopa in carbidopa-pretreated rats than in control rats. Norepinephrine N-Methyl-transferase activity assayed in vitro was markedly inhibited by SAH; the inhibition was competitive with SAMe as the variable substrate and the Ki for SAH was 1.9 x 10(-5) M. Increasing the SAH/SAMe ratio in in vitro experiments sharply reduced norepinephrine N-methyltransferase activity. The apparent inhibition of hypothalamic epinephrine synthesis in vivo after L-dopa injection is suggested to be a consequence of the increased SAH/SAMe ratio.

Animals↗
PubMed1982

Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia.

Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Ionophore (A23187)-induced efflux of [3H]norepinephrine and endogenous norepinephrine in the rat vas deferens.

The calcium ionophore, A23187, produced a concentration-dependent increase in the release of norepinephrine from nerves in the rat vas deferens. Maximum response to A23187 (10(-6) - 10(-5) M) was delayed in onset, occurring 60-80 min after initiation of continuous superfusion with A23187. In fact. after tissue exposure to A23187 (10(-5) M) for only 5 min with subsequent superfusion in A23187-free buffer, a significant but delayed increase in norepinephrine efflux occurred. The A23187-induced increase in efflux of norepinephrine was not altered when neuronal sodium conductance was blocked with tetrodotoxin (3.1 X 10(-7) M) or when Na+, K+ -stimulated ATPase was blocked with ouabain (10(-4) M). Release of norepinephrine by A23187 was calcium-dependent since A23187-induced efflux of norepinephrine was diminished (approximately 50%), although not abolished, in calcium-free buffer. Thus, one component of A23187 action was calcium independent. A23187 caused an increased efflux of both norepinephrine formed endogenously and [3H]norepinephrine taken up into neuronal stores. However, the effects of A23187, both on rate and maximum amount of release were greater for [3H]norepinephrine than for endogenous norepinephrine. The present studies demonstrate that neurotransmitter efflux can be induced by carboxylic ionophores in a calcium-dependent process, and this approach may prove useful in studies evaluating factors that modulate neurotransmitter release processes.

Animals↗
PubMed1981

Role of serotonin in the hypothalamic regulation of pituitary function.

Serotonin is only one of numerous neurotransmitters that may have roles in the regulation of pituitary secretion. The literature pertaining to serotoninergic involvement in the hypothalamic control is large, and a report of this type cannot provide a comprehensive review of that literature. Instead, the data presented and the literature cited were intended to be illustrative of the use of drug intervention and other techniques for probing the role of serotonin in the regulation of pituitary secretion. Clearly further studies with each of the pituitary hormones are needed, and the development of drugs acting on serotonin neurons with greater specificity can be a strong impetus to progress in this research area.

5-Hydroxytryptophan↗
PubMed1981

Repeated administration of pergolide to rats attenuates the acute elevation of serum corticosterone by pergolide.

A single injection (0.3 mg/kg IP) of pergolide mesylate, a dopamine agonist, increased serum corticosterone concentration several-fold in rats. This increase did not occur or was greatly diminished in rats that had received four previous daily injections of pergolide. The non-responsiveness to pergolide persisted at the second day after the last of 4 daily injections of pergolide, but by the third and fourth days the rats were again responsive to pergolide in terms of serum corticosterone elevation. The lowering of dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) by pergolide occurred in pergolide-pretreated rats to the same extent as in control rats. Serum corticosterone concentration in pergolide-pretreated rats was elevated normally by a serotonin agonist, quipazine. Since the pituitary-adrenocortical system can be activated in pergolide-pretreated rats (indicated by the normal response to quipazine), the insensitivity to pergolide may be due to decreased responsiveness of central dopamine receptors mediating corticosterone elevation by pergolide.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Purkinje cell loss and the noradrenergic system in the cerebellum of pcd mutant mice.

Purkinje cells in the cerebellum receive inhibitory noradrenergic input from the locus coeruleus. In pcd mutant mice all Purkinje cells degenerate by 45 days of age. The purpose of the present studies was to determine if the loss of these cerebellar neurons affects the amounts of norepinephrine in the cerebellum of mice 25-280 days of age. No significant changes in norepinephrine content were detected during or after Purkinje cell degeneration. However, since degeneration led to a reduction in cerebellar weight, the norepinephrine concentration was increased in pcd mutants. These results indicate that despite the loss of a major postsynaptic target (Purkinje cells), the cerebellar noradrenergic input remains stable.

Age Factors↗