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Biomedical subjects

J M Rabey

Publications and source records attributed to J M Rabey.

At least 73 records · Page 4Linked to original sources
PubMed1986

Dopaminergic modulation of the septo-hippocampal cholinergic system activity under stress.

The effects of the dopaminergic agonist apomorphine or the antagonist sulpiride on high affinity choline uptake and newly synthesized acetylcholine release by hippocampal synaptosomal preparations, were examined in rats subjected to immobilization stress. Increased dopamine uptake by septal synaptosomal preparations was taken as evidence for increased mesoseptal dopaminergic activity in response to stress. While apomorphine treatment failed to alter choline uptake or acetylcholine release in unhandled rats, it did however prevent the stress-induced increase in these cholinergic parameters. In contrast, after treatment with sulpiride both choline uptake and acetylcholine release were increased in unhandled rats, as they were after acute stress. Acute stress of sulpiride treated rats however resulted in changes similar to those produced by administration of either sulpiride or stress separately. We conclude that the mesoseptal dopaminergic system plays an important role in modulating the activity of the septo-hippocampal cholinergic system under stress.

Acetylcholine↗
PubMed1986

Cholinergic muscarinic binding by rat lymphocytes: effects of antagonist treatment, strain and aging.

Cholinergic muscarinic binding by viable peripheral lymphocytes was assessed by measuring specific binding of the muscarinic antagonist [3H]quinuclidinyl benzylate. After atropine treatment maximal lymphocyte muscarinic binding was increased by about 30%, as it did in the hippocampus of the same rats. Strain-dependent differences in muscarinic binding by peripheral lymphocytes were correlated with similar differences in selective brain regions. Higher muscarinic binding was observed in lymphocytes derived from aged (24 months old) rats. We conclude: atropine treatment causes an increase in lymphocyte muscarinic binding as it does in the brain; strain differences in brain muscarinic binding are paralleled by similar differences in lymphocytes; and in aged rats muscarinic binding capacity by lymphocytes is elevated. The results indicate that circulating lymphocytes may serve as a useful peripheral marker reflecting induced alterations or inherent differences in muscarinic binding.

Aging↗
PubMed1986

Cholinergic muscarinic binding by human lymphocytes: changes with aging, antagonist treatment, and senile dementia of the Alzheimer type.

In peripheral blood lymphocytes (mixed lymphocytes isolated on a Ficoll-Hypaque density gradient) derived from normal human subjects, cholinergic muscarinic binding capacity was found to increase with age. In contrast, lymphocytes derived from patients with "probable" senile dementia of the Alzheimer type (SDAT) exhibited a marked reduction in binding capacity. Treatment of these patients with antimuscarinic drugs was associated with increased muscarinic binding by lymphocytes. These results indicate that cholinergic muscarinic binding by peripheral blood lymphocytes may be useful in the study of alterations associated with aging and SDAT, as well as in evaluating changes induced by certain cholinergic drug treatments.

Aging↗
PubMed1986

Selective regional effect of various neuroactive drugs on bromocriptine concentration in the brain of rats.

Bromocriptine (2-Br-alpha-ergocryptine), a partial ergoline derivative, is a dopamine agonist which has been used successfully in the treatment of hyperprolactinemia, acromegaly and Parkinson's disease. The main targets for the action of the drug are the hypothalamic, hypophyseal pathway and the striatum. These regions contain different populations of neurons which interact with each other in a complex way. In order to check the mechanism of these interactions in rats, we administered different neuroactive drugs together with bromocriptine. After a single intraperitoneal injection, bromocriptine concentration in the striatum was 13.1 +/- 2.9 ng/mg protein, and in the hypothalamus 13.9 +/- 0.8 ng/mg protein. The largest increase in the bromocriptine content in the striatum was found after the concomitant administration of naloxone, an opiate receptor blocker (21.2 +/- 2.5 ng/mg protein). The largest increase of the bromocriptine content in the hypothalamus was found after the concomitant injection of methysergide, a serotonin receptor blocker (27.8 +/- 2.6 ng/mg protein). Amantadine, diazepam and haloperidol caused the largest decrease in the two regions. The mechanism of interaction and therapeutic implication of these findings are discussed.

Amantadine↗
PubMed1985

Dynamics of cholinergic synaptic mechanisms in rat hippocampus after stress.

Changes in high affinity [3H]choline uptake, newly synthesized [3H]acetylcholine release and [3H]quinuclidinylbenzilate (QNB) binding were characterized in crude synaptosomal preparations from rat hippocampus immediately after different intervals of immobilization stress and at different times following chronic intermittent stress (2h once daily for 5 days). Choline uptake was increased to 125% of unhandled controls after 10 min of stress, after 2 h it returned to control levels and after chronic stress uptake was reduced to 75% of control. Acetylcholine release was enhanced after all stress intervals. Maximal muscarinic (QNB) binding capacity (Bmax) was increased to 135% of control only after chronic stress, with no change in Kd values. Following chronic stress the changes observed in cholinergic synaptic mechanisms all persist for up to 2 days. Recovery occurred only by the 7th post-stress day. We conclude: presynaptic hippocampal cholinergic terminals are rapidly activated by stressful stimuli and this is expressed by an increase in choline uptake and newly synthesized acetylcholine release; after prolonged periods of stress adaptive changes in the cholinergic terminals are expressed by a reduction in choline uptake and an elevation in the number of muscarinic binding sites; and the chronic stress-induced changes are slow to recover. The results demonstrate that the septo-hippocampal cholinergic system is an integral part of the adaptive response to stress.

Acetylcholine↗
PubMed1984

Effect of various neuroactive drugs on bromocriptine concentration in the striatum of rats.

Parkinsonian patients are usually given several drugs concomitantly with bromocriptine, with variable results. The possibility of interference of these drugs with the availability of bromocriptine in the brain was investigated by measuring bromocriptine concentrations in the striatum in rats. After a single injection, bromocriptine concentration in the striatum was 13.1 +/- 2.9 ng/mg protein. Naloxone, an opiate receptor blocker, was found to produce the largest increase in bromocriptine content (21.7 +/- 2.5 ng/mg protein). Amantadine, diazepam and haloperidol produced the largest decreases (3.2 +/- 0.9, 3.3 +/- 0.8 and 4.4 +/- 1.2 ng/mg protein, respectively). Rats given L-dopa or benzodiazepine also showed slightly lower levels of bromocriptine.

Animals↗
PubMed1983

Strain-dependent and stress-induced changes in rat hippocampal cholinergic system.

The study demonstrates that in the hippocampus of inbred Wistar-Kyoto (WKY) rats [3H]choline uptake is 38% higher than in Brown-Norway (BN) rats. In contrast, the maximum binding capacity of [3H]quinuclidinylbenzilate (QNB) is 28% lower in WKY than in BN rats. After immobilization stress there is a reduction in [3H]choline accumulation which is more pronounced in WKY rats. Furthermore, maximal QNB binding after stress is increased only in WKY rats. Choline acetyltransferase activity, which was 83.5% higher in WKY rats, was not altered after stress in both strains. We conclude that: (1) choline accumulation is directly related to choline acetyltransferase activity in hippocampal synaptosomes; (2) maximum cholinergic muscarinic binding capacity is inversely related to the above two presynaptic activities and (3) immobilization stress results in a decreased choline accumulation and may lead to an increased QNB binding. The results imply that reduction in choline accumulation may be a compensatory mechanism of cholinergic synapses during adaptation to lengthly periods of neuronal activity.

Animals↗
PubMed1983

Convulsive attacks due to antidepressant drug overdoses: case reports and discussion.

Antidepressant drug overdoses have been reported to induce seizures, but the etiology of this phenomenon is still unclear. Recently we treated three patients who suffered from epileptic seizures after acute overdoses of three antidepressant drugs: (a) Dibenzepin HCl (Noveril), (b) Maprotiline HCl (Ludiomil), and (c) Clorimipramine (Anafranil). After a review of the pertinent literature, the possible role of antidepressant drugs in the genesis of epileptic seizures is discussed.

Adult↗
PubMed1981

The regulation of striatal DOPA synthesis by alpha 2-adrenoreceptors.

The administration of alpha 2-adrenoreceptor antagonists SKF 64139 or SKF 72223 (TIQ derivatives) elicits an increase in striatal DOPA synthesis. The findings that the enhanced DOPA synthesis is reversed by pretreatment of the animals with clonidine or with the D beta H inhibitor FLA-63 suggest that action of the TIQ derivatives is related to their ability to block alpha-adrenoreceptors. It is being postulated that the enhanced striatal DOPA synthesis elicited by the TIQ derivatives is a result of inhibition of dopaminergic neurotransmission.

Adrenergic beta-Antagonists↗
PubMed1981

Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by partial ergoline.

The capacity of the ergoline, pergolide, and of the partial ergoline, LY 141865, to stimulate pre- and postsynaptic dopamine (DA) receptors was investigated. Binding studies have revealed that pergolide has a high affinity, while the partial ergoline, LY 141865, has a low affinity for the postsynaptic striatal DA receptors in vitro. Two behavioral animal models were used to assess the DA agonist potencies of these compounds for the postsynaptic DA receptors in vivo. Pergolide induced turning behavior in rats with 6-hydroxydopamine (6-OH-DA) lesions, and relief of tremor in monkeys with ventromedial tegmental lesions, at a lower dose and for a longer duration than LY 141865. An in vivo and an in vitro biochemical test was use to measure the ability of these compounds to stimulate presynaptic DA receptors. In the in vitro test, pergolide and LY 141865 were found to have low inhibitory activity for synaptosomal tyrosine hydroxylase, while in the in vivo test, both drugs were effective even in low doses in reversing the gamma-butyrolactone elicited increased accumulation of striatal DOPA. These results suggest that pergolide has a high affinity for pre- and postsynaptic DA receptors, while its partial ergoline analogue has a high affinity for the presynaptic, but not for the postsynaptic DA receptors. The data also suggest that dopamine synthesis in vitro and in vivo may be regulated by different presynaptic DA receptors.

Animals↗
PubMed1981

Dissociation of thyrotropin and prolactin responsiveness to thyrotropin releasing hormone stimulation in L-dopa treated parkinsonian patients.

The hPRL, hTSH and T3 response to thyrotropin releasing hormone (TRH) stimulation (200 microgram i.v.) were studied in 8 parkinsonian patients under chronic L-dopa-carbidopa therapy. In 6 out of the 8 patients studied, treatment was stopped for a period of 2 weeks and the TRH stimulation test was repeated under similar experimental conditions. In the L-dopa-carbidopa treated patients basal hTSH levels and the hTSH response to TRH were significantly suppressed. By contrast, in the 6 patients 2 weeks after cessation of treatment, although basal hTSH levels were still suppressed, a normal hTSH response to TRH was observed. Neither the basal T3 and T4 concentrations, nor the T3 response to TRH were affected by the L-dopa-carbidopa treatment. In addition, basal hPRL levels as well as the hPRL: response to TRH were within the normal range in the two groups of patients studied. Our study provides further support for a dopaminergic inhibitory action on the hypothalamo-hypophyseal-thyroidal axis (HHTA). The inhibition of basal hTSH secretion and th hTSH response to TRH by L-dopa, suggest that the blocking action of dopamine is exerted at the hypothalamic as well as at the pituitary level. In our hands, chronic administration of L-dopa did not affect either tonic hPRL secretion of the hPRL response to TRH. The dissociation or response to TRH under the same inhibitory action of dopaminergic stimulation can be interpreted as demonstrating a greater sensitivity of the pituitary thyrotrophs, than the prolactin secreting cells, to the blocking effect of dopamine.

Aged↗
PubMed1980

L-dopa and the secretion of sebum in Parkinsonian patients.

Sebum secretion was studied in 14 parkinsonian patients before and after 3 months of treatment with L-dopa. An abnormality of sebum secretion was shown to exist in parkinsonism. In 7 patients, successfully treated with L-dopa, sebum secretion diminished and its pattern improved. In all patients, in whom L-dopa treatment did not result in noticeable clinical changes, there was no significant modification in sebum secretion. No change was observed in the secretion of sebum of 5 normal control subjects, who were given L-dopa for 1 week.

Adult↗