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G M Rose

Publications and source records attributed to G M Rose.

79 records · Page 5Linked to original sources
PubMedDate not supplied

Age-related alterations in monoamine release from rat striatum: an in vivo electrochemical study.

In vivo electrochemistry was used to examine presynaptic alterations in dopamine release in the striatum of aged rats. Chronoamperometric determinations of monoamine release, induced by local micro pressure-ejection of K+, were made using Nafion-coated graphite epoxy electrodes. Recordings were made from the striatum of urethane-anesthetized Fischer 344 rats at 6, 24, and greater than or equal to 29 months of age. Following the in vivo electrochemical experiments, the animals were sacrificed and the caudate nucleus removed for analysis of whole tissue levels of monoamines and their metabolites using standard HPLC techniques. Overall, mean amplitudes of K+-evoked releases from the striatum of 6 month and 24 month F344 rats did not differ significantly (p greater than 0.1). However, this result was complicated by the observation that the mean values obtained from two separate groups of 24 month animals, recorded 6 months apart, were significantly different from each other (p less than 0.001). Mean releases for the later 24 month group were significantly less than for the 6 month group (p less than 0.01). No difference was found in the release magnitudes of 6 month animals recorded contemporaneously with the two groups of 24 month rats. Release amplitudes for the greater than or equal to 29 month group were clearly less than from the 6 month animals (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
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Increased responsiveness of hippocampal pyramidal neurons to nicotine in aged, learning-impaired rats.

The effect of aging upon the responsiveness of hippocampal CA1 pyramidal neurons to nicotine was investigated using electrophysiological techniques in male Fischer 344 rats. Prior to electrophysiological recording, animals were behaviorally tested using the Morris water maze. All 3-6 and 18-21 month rats displayed rapid place learning in this task, while none of the 27-30 month animals learned within the 5-day test period. By contrast, rats of all age groups were able to learn a cue version of the water maze task. Following behavioral testing, the animals were anesthetized with sodium pentobarbital for acute recording. Nicotine was locally applied to electrophysiologically identified CA1 pyramidal neurons using pressure microejection from two-barreled glass microelectrodes. For each neuron, a dose of nicotine was found which elicited a 300-400% increase in basal firing rate. These data were used to construct cumulative dose response curves for populations of neurons tested in 3-6-, 18-21-, and 27-30-month-old animals. An age-related increase in the responsiveness of CA1 pyramidal neurons to locally applied nicotine was observed. The results of this study suggest that an increase in hippocampal CA1 pyramidal cell responsiveness to nicotine could be related to the impaired place learning ability seen with aging.

Action Potentials↗
PubMedDate not supplied

Age-related reduction in responses of rat hippocampal neurons to locally applied monoamines.

Age-related changes in the responsiveness of hippocampal pyramidal neurons to norepinephrine (NE) and serotonin (5HT) were investigated using electrophysiological techniques. Local application of each monamine via pressure micro-ejection was employed to establish the dose which elicited a 50% change in spontaneous discharge rate of single pyramidal neurons; these data were used to construct dose response curves for the population of neurons tested in 3-6, 11-13, 18-20, and 27-30 month old rats. The percentage of cells responding in rats 18-20 and 27-30 months old decreased for both NE and 5HT. There was also a progressive increase with age in the population ED50 for 5HT starting at 18-20 months. For neurons which demonstrated a response to NE, no decrease in the population ED50 was observed. Taken together these data indicate that there is a progressive age-related decline in the postsynaptic response to NE and 5HT in the rodent hippocampus.

Action Potentials↗
PubMedDate not supplied

Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function.

L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5 mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated using a sensorimotor battery, a motor-learning task, and the Morris water maze. At 118 weeks of age, cerebellar noradrenergic function was evaluated in the surviving rats using in vivo electrochemistry. The rats were then sacrificed to measure brain monoamine oxidase activity and perform quantitative autoradiography to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A clear effect of chronic deprenyl treatment upon longevity was not observed. Several measures of CNS function were altered in the deprenyl-treated animals: 1) spatial learning in the Morris water maze was improved; 2) electrochemical signals recorded following local application of NE were reduced, and the responsiveness to the reuptake blocker nomifensine was enhanced, in the cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding affinity was enhanced. In contrast, chronic deprenyl treatment did not cause changes in: 1) sensorimotor function, as evaluated by balance beam, inclined screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor density in any region examined except for the inferior colliculus, or binding affinity in any region examined; or 4) striatal D2 dopamine receptor number or affinity. Thus, long-term oral administration of deprenyl extended the functional life span of rats with respect to cognitive, but not motor, performance.

Animals↗
PubMedDate not supplied

Bioavailability of single and multiple doses of enteric-coated mesalamine and sulphasalazine.

The bioavailibity of mesalamine from enteric-coated mesalamine and sulphasalazine was determined following a single dose and at steady state in healthy subjects in crossover studies. Plasma concentrations and urinary excretion of mesalamine and its major metabolite, N-acetyl-5-aminosalicylic acid, were measured. After a single dose of enteric-coated mesalamine, about 10 h elapsed before the onset of measurable plasma drug concentrations, probably representing gastro-intestinal transit prior to drug release near the ileocaecal junction. The elimination kinetics were similar for a single oral dose and steady state using enteric-coated mesalamine, but after both single and multiple administration of enteric-coated mesalamine only about 20% of the mesalamine given was absorbed, with about 80% estimated to remain for colon therapeutic activity. It is concluded that, despite different mechanisms of mesalamine release, enteric-coated mesalamine and sulphasalazine produced similar mesalamine absorption.

Administration, Oral↗
PubMedDate not supplied

Development of an intact blood-brain barrier in brain tissue transplants is dependent on the site of transplantation.

Transplantation of fetal septal forebrain tissue was performed to the anterior chamber of the eye, or intracranially to the rostral hippocampal formation in rats, to evaluate the impact of transplantation site on the development of an intact blood-brain barrier (BBB). The tissue was studied at 1,2,3, and 4 wk following transplantation by means of intravenous injection of Trypan blue, which is a vital stain not normally penetrating the BBB, as well as with an antibody specifically directed against the rat BBB, SM171. In the intraocular septal transplants, there was a significant leakage of Trypan blue 1 wk postgrafting, associated with a few laminin-immunoreactive blood vessels that did not contain any SM17I-immunoreactivity. However, at 2 wk postgrafting, the intraocular grafts exhibited an extensive plexus of thin-walled blood vessels expressing SMI71 immunoreactivity and no Trypan blue leakage. Thus, it appeared that a BBB had developed to some degree by 2 wk postgrafting in oculo. In the intracranial grafts, on the other hand, Trypan blue leakage could be seen as long as 3 wk postgrafting, and a dense plexus of blood vessels with SMI71 immunoreactivity was first seen at 4 wk postgrafting. Thus, the development of Trypan blue impermeability was delayed with 1 to 2 wk in the intracranial versus the intraocular grafts. Control experiments using psychological stress in adult rats as a means to transiently disrupt the BBB revealed that an increase in Trypan blue leakage correlated well with the disappearance of SMI71 immunoreactivity. Taken together, these studies demonstrate that the site of transplantation can influence the development of an intact BBB in neural tissue grafts.

Animals↗