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Biomedical subjects

R Laverty

Publications and source records attributed to R Laverty.

17 recordsLinked to original sources
PubMed1992

The infusion of an NMDA antagonist into perirhinal cortex suppresses amygdala-kindled seizures.

The seizure-modulating role of N-methyl-D-aspartate (NMDA) receptors located in several limbic areas was investigated. Amygdala-kindled rats were microinfused with the selective NMDA-receptor antagonist 2-amino-5-phosphonovalerate (APV, 1 microliter, 70 nmol) or artificial cerebrospinal fluid (ACSF) applied through a cannula located in either the amygdala or perirhinal, pyriform or deep prepyriform cortices. APV infused into the stimulation site raised the threshold for seizure generation. Surprisingly, APV infused into perirhinal cortex, but not into other regions, also dramatically suppressed behavioural seizures and afterdischarges (AD) elicited 5 min after the infusion. If stimulus intensities were markedly elevated however, the seizure suppression was overcome. This latter effect was reversible and repeatable, as seizures and AD were reliably reinstated when these animals were stimulated after infusion with ACSF. A similar effect, whereby perirhinal infusions blocked seizure activity, was also demonstrated in an animal kindled from the olfactory bulb and in one kindled from the perforant path. These results suggest that NMDA receptors located in the perirhinal cortex may play a major role in the modulation of AD activity elicited from more distal brain regions. Furthermore, activation of perirhinal cortex may be a critical requirement for the generation of amygdala-stimulated AD in the kindled animal.

2-Amino-5-phosphonovalerate↗
PubMed1992

Changes in brain amine levels associated with the morphological and behavioural development of the worker honeybee.

Changes in biogenic amine levels associated with the morphological and behavioural development of the worker honeybee are examined. A significant increase in amine levels in the head of the honeybee is associated with transition from the larval to pupal stage. Adult emergence is also accompanied by a significant increase in 5-HT levels in the brain, but no significant change in brain dopamine (DA) levels. NADA (N-acetyldopamine) levels increase during larval and pupal development, but in contrast to both DA and 5-HT, drop significantly during the transition from pupa to adult. Levels of DA in the brain of nectar and pollen forager bees, presumed to be among the oldest adults sampled, were found to be significantly higher than in nurses, undertakers or food storers. These results suggest that an age-dependent change in amine levels occurs in the brain of the worker bee. In the optic lobes, levels of DA and 5-HT were found to be significantly higher in pollen forager bees than in all other behavioural groups. Significant differences in amine levels in the optic lobes of nectar foragers and pollen foragers indicate that some differences in amine levels occur independent of worker age. The functional significance of differences in brain amine levels and whether or not biogenic amines play a direct role in the control of honeybee behaviour has yet to be established.

Aging↗
PubMed1991

3,4-Methylenedioxymethamphetamine induces Fos-like proteins in rat basal ganglia: reversal with MK 801.

Injections of 3,4-methylenedioxymethamphetamine (MDMA, 25 mg/kg, i.p.) to rats lead to an accumulation of c-fos protein (Fos) and Fos-related antigens in caudate-putamen, nucleus accumbens and olfactory tubercle. This induction occurred at least 2 h (but not at 10 min) after injection and Fos levels had returned to baseline after 24 h, although Fos-related antigens remained elevated 24 h after injection. The NMDA antagonist MK 801 inhibited Fos and Fos-related antigen induction after MDMA injections, whereas fluoxetine, a serotonin uptake inhibitor, had no effect. Thus, MDMA induces Fos and Fos-related antigens in striatal neurons in an NMDA-reversible fashion.

3,4-Methylenedioxyamphetamine↗
PubMed1990

The N-methyl-D-aspartate antagonists aminophosphonovalerate and carboxypiperazinephosphonate retard the development and expression of kindled seizures.

To investigate the possible role of N-methyl-D-aspartate (NMDA) receptors in the development and expression of amygdaloid-kindled seizures, rats were either chronically infused with 2-amino-5-phosphonovalerate (APV, 20-40 mM) or pre-injected with carboxypiperazine-phosphonate (CPP, 1-10 mg/kg), both selective NMDA-receptor antagonists, and then kindled from the amygdala. At the higher dose (40 mM), APV blocked the induction of long-term potentiation in the dentate gyrus. APV also retarded clinical seizure development dose-dependently and increased seizure thresholds without affecting afterdischarge (AD) duration. These same doses of APV had only small anticonvulsant effects on established kindled seizures. Although CPP (1-10 mg/kg) had no effect when rats were kindled 45 min after injection it dose-dependently retarded focal and generalization stages at the 150 min injection-kindling interval. Once relieved of drug, animals proceeded to develop stage 5 seizures with shorter duration ADs than saline-control animals. When the previously-kindled, saline groups were crossed to CPP a small depressant effect on seizure expression was observed. These results suggest that NMDA receptors are primarily involved in kindling development rather than in maintaining the kindled state.

2-Amino-5-phosphonovalerate↗
PubMed1990

Effects of ethanol and Ro 15-4513 in an electrophysiological model of anxiolytic action.

Previous research has implicated hippocampal rhythmical slow activity in the mechanisms of action of the anxiolytic drugs. In this study ethanol and a putative ethanol antagonist, Ro 15-4513, were investigated with reticular elicitation of rhythmical slow activity. Doses of ethanol between 0.6 and 3.1 g/kg were used. Ethanol reduced the frequency of reticular-elicited rhythmical slow activity in the same way as has been reported for anxiolytic barbiturates and benzodiazepines. This effect was linearly related to log dose of ethanol in the range of 1.7-3.1 g/kg. Ro 15-4513 at a dose of 2 mg/kg reduced the effect of ethanol (2.0 g/kg) but had no action itself. Ethanol also decreased the slope of the stimulation voltage-rhythmical slow activity frequency function but this effect was not reduced by Ro 15-4513. These results show that ethanol acts in a similar manner to conventional anxiolytic drugs but that only one component of this action can be reduced by Ro 15-4513.

Animals↗
PubMed1989

Dose-dependent reduction by Ro 15-4513 in mice of the effects of ethanol and some other general depressant drugs.

In mice, Ro 15-4513 reduced the anaesthesia induced by ethanol and some other general depressant drugs, but was less effective against others. The order of potency was, from greatest reduction to least, ethanol, t-butanol, trichloroethanol, urethane, chlormethiazode, pentobarbitone. Of the two gaseous anaesthetics that were tested, ether anaesthesia was reduced but halothane was not. These results appeared independent of the doses of depressant or of Ro 15-4513; the effect of Ro 15-4513 in reducing ethanol anaesthesia was blocked by flumazenil (Ro 15-1788). It would appear that the benzodiazepine receptor complex is of importance in the induction of anaesthesia, most significantly with ethanol and to a diminishing degree with the other general depressants tested.

Anesthetics↗
PubMed1979

Clonidine reversal of increased norepinephrine metabolite levels during morphine withdrawal.

The production of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) in brain regions innervated by the locus coeruleus was increased during naloxone-precipitated withdrawal from chronic morphine treatment. This MHPG increase was reversed by subcutaneous administration of clonidine. Changes in MHPG levels paralleled the elctrophysiological changes found by Aghajanian (1978) in locus coeruleus firing rate with similar treatments, demonstrating the usefulness of MHPG changes as an index of central noradrenergic function.

Animals↗
PubMed1979

Metabolic and pharmacodynamic tolerance to ethanol in rats.

The development of tolerance to ethanol was studied in rats fed nutritionally adequate liquid diets containing ethanol or sucrose for up to 5 weeks. Tolerance was shown to be due to both metabolic and pharmacodynamic factors. Tolerance began to develop after 3 days of ethanol intake, reached a plateau by 16 days and persisted for up to 22 days after stopping the ethanol intake. The rate of onset and decay of both components of tolerance was similar.

Alcohol Drinking↗
PubMed1979

Physical dependence following prolonged ethanol or t-butanol administration to rats.

Rats were fed on liquid diets containing ethanol or t-butanol. On removal of either alcohol from the diet after 4-20 days, withdrawal reactions were observed. The range of withdrawal signs produced by the two alcohols were identical although the time course of the withdrawal reactions differed. Administration of one alcohol prevented the appearance of a withdrawal reaction in rats dependent on the other alcohol. Depletion of brain noradrenaline and dopamine did not prevent the development of physical dependence on either alcohol. Thus, neither aldehyde formation nor brain catecholamines appear to be involved in the development of physical dependence on these alcohols.

Alcoholism↗
PubMed1978

Brief communication. Inability of hexamethonium to block the discriminative stimulus (SD) property of nicotine.

Rats were trained to discriminate between levers on a white or black wall to obtain food reinforcement, using nicotine or saline administration as the discriminative stimulus (SD). When hexamethonium was administered, either peripherally or intraventricularly, before the nicotine injection these rats responded as though they had received nicotine alone. This indicates that nicotine receptors responsible for its SD property are not blocked by hexamethonium, or alternatively that it is necessary to block the peripheral and central actions simultaneously to completely eliminate the cueing effect of the nicotine injection.

Animals↗
PubMed1978

Catecholamines: role in health and disease.

The naturally occurring catecholamines, noradrenaline, adrenaline and dopamine, have been found in a wide range of animal and vegetable tissues, but are particularly associated with nervous tissue in animals. Of the many processes affecting the response to stimulation of catecholamine containing nerves, the synthesis of catecholamines, particularly the first enzymatic stage involving tyrosine hydroxylase, and the re-uptake process, whereby the nerve recovers much of the released catecholamine, appear to be the most significant. In peripheral tissues noradrenaline appears to be involved predominantly in the sympathetic control of blood pressure and flow while adrenaline is more important to metabolic processes especially fat and glucose turnover. Both may be released in increased amounts by various stimuli that cause stress or arousal in the body. Dopamine has not yet been shown to have any significant physiological function in peripheral tissues. In the central nervous system, noradrenaline and dopamine are the two main catecholamines. The working of the brain is complex and involves balanced interactions between a variety of neurotransmitters, known or as yet unrecognised. However, noradrenaline appears to play a role in the central control of blood pressure, and in determining mood and activity probably by affecting the emotional drives. Dopamine is certainly important in the control of motor pathways, as shown by the dopamine deficiency syndrome in Parkinson's disease, and is possibly of significance in the abnormal behaviour of psychotics. The role of the small concentration of adrenaline in the brain has yet to be fully established.

Catecholamines↗
PubMed1976

Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment.

Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (60HDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 60HDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 60HDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla.

Animals↗
PubMed1975

Mechanisms of selective depletion of brain regional noradrenaline by systemic 6-hydroxydopamine in newborn rats.

6-Hydroxydopamine injected systemically into newborn rats caused permanent depletions of the noradrenaline content of only certain brain regions. When 6-hydroxydopamine was given i.p. on days 1 and 2 after birth only the cortex, hippocampus and spinal cord were permanently depleted. 6-Hydroxydopamine given on days 9 and 10 after birth caused a permenent depletion predominantly from the cerebellum. Other regions were unaffected or were depleted for 4 days or less. The hypothalamus showed a gradual recovery of noradrenaline levels over a period of more than 20 days after injection, suggesting that only in this region was the apparent lack of effect of 6-hydroxydopamine due to neuronal regrowth. 6-Hydroxydopamine appeared to gain access to all regions except the pons-medulla when injected up to 10 days after birth, since at least temporary effects on noradrenaline storage were observed. 3H-Noradrenaline after i.p. injection was found in similar relative amounts in all brain regions in rats up to 20 days old. Thus regional differences due to age in the ability of 6-hydroxydopamine to reach various brain regions apparently do not explain the selective susceptibility to permenent depletion. It is suggested that the selective depletion must be due to interactions between the maturity of the adrenergic neurones and other factors such as their ability to take up or retain the 6-hydroxydopamine.

Aging↗
PubMed1975

Programmatic computer simulation model for medical school planning.

A comprehensive programmatic computer simulation planning model for a school of medicine was generated by integrating several separate simulation models with on-site cost study information. An elementary validation of the model was achieved. The model generated program costs in terms of both faculty hours and dollars. Results indicated that the size of the medical class could be increased from 75 to 100 students within the present resource limitations by transferring faculty time to education from other programs. The maximum class size was limited by the availability of clinical material. The basic science departments could handle this class size easily without significant reduction in other programs, but the clinical departments could not do so unless inpatient levels increased significantly.

Computers↗