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Biomedical subjects

K E Moore

Publications and source records attributed to K E Moore.

At least 163 records · Page 9Linked to original sources
PubMed1982

Tolerance develops to the haloperidol-induced increase in the efflux of dopamine metabolites from the brains of unanesthetized, freely-moving rats.

The lateral cerebral ventricles of freely moving rats were perfused by means of chronically implanted push-pull cannulae every second day for 2 weeks. Perfusates were analyzed for metabolites of dopamine [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] and of 5-hydroxytryptamine [5-hydroxyindoleacetic acid (5HIAA)] using high performance liquid chromatography and an amperometric detector. Rats received daily subcutaneous injections of haloperidol (1 mg/kg) or its vehicle. After the first injection of haloperidol the concentrations of DOPAC and HVA were markedly increased while that of 5HIAA was unchanged. Complete tolerance developed to the haloperidol-induced increased efflux of dopamine metabolites by day 9, although a higher dose of haloperidol (2 mgf/kg) on day 15 was still capable of eliciting a modest increase in the efflux of DOPAC and HVA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Dopaminergic neuronal function, anterior pituitary dopamine content, and serum concentrations of prolactin, luteinizing hormone and progesterone in the aged female rat.

The serum concentrations of prolactin (PRL), progesterone and luteinizing hormone (LH), and the content and rate of synthesis of dopamine (DA) in selected brain regions were determined in young (3-6 months), intermediate (13-15 months) and aged (24-25 months) female Long-Evans rats. Young rats were examined on the days of diestrus 2 and estrus. Intermediate rats were divided into 2 groups, a group which was cycling regularly (examined on the day of estrus) and a group which exhibited constant estrus. Aged rats were divided into 3 groups one which cycled regularly (examined on day of estrus), one which exhibited constant estrus, and one which exhibited repetitive pseudopregnancies. Serum PRL was increased in all intermediate and aged rats when compared to values in young animals. Serum LH was increased and progesterone decreased in those intermediate and aged rats which exhibited constant estrous reproductive patterns. The DA content was generally decreased in the median eminence, posterior pituitary, striatum, nucleus accumbens and olfactory tubercle of all aged rats, while the rate of DA synthesis was decreased only in the median eminence of aged, non-cycling rats. This suggests that all DA neuronal systems except those in the tuberoinfundibular system are able to compensate for the age-related loss. Despite the apparent reduction of tuberoinfundibular DA neuronal function the concentration of DA in the anterior pituitary, which is believed to represent amine released from the neurons, is dramatically increased in intermediate age rats in constant estrus, and in all groups of aged rats. The maintenance of high PRL secretion despite the elevated content of DNA in the anterior pituitary suggests an age-related defect in the dynamics of DA in this gland; this defect may contribute to the loss of reproductive function in the aging rat.

Aging↗
PubMed1982

Measurement of metabolites of dopamine and 5-hydroxytryptamine in cerebroventricular perfusates of unanesthetized, freely-moving rats: selective effects of drugs.

A method was developed for measuring endogenous acid metabolites of dopamine (dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA) and of 5-hydroxytryptamine (5-hydroxyindoleacetic acid, 5HIAA) in serial samples of cerebroventricular perfusates from unanesthetized, freely-moving rats by the use of high performance liquid chromatography with electrochemical detection. Systemic administration of probenecid increased while pargyline reduced the efflux of all of the acid metabolites. Intraperitoneal injection of L-tryptophan increased the perfusate content of 5HIAA, decreased HVA and was without effect on DOPAC. Injections of haloperidol increased the efflux of DOPAC and HVA but did not alter the efflux of 5HIAA. Administration of apomorphine decreased the concentration of all three compounds. These drug-induced changes are generally consistent with those reported to occur in brain tissues. The results indicate that this method can be employed to monitor the activity of dopamine and 5-hydroxytryptamine neurons in unanesthetized, freely-moving rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Effects of prolactin on central dopaminergic neurons.

The activities of various dopaminergic neurons in the brain have been estimated biochemically by quantifying the rate of synthesis or turnover of dopamine in brain regions containing the terminals of these neurons. In addition, the activity of tuberoinfundibular dopaminergic neurons have been estimated from the concentration of dopamine in pituitary stalk blood. Manipulations which increase concentrations of prolactin in cerebrospinal fluid or serum (systemic or intracerebroventricular injections of prolactin; injections of dopaminergic antagonists or estrogens; implantation of pituitaries under the renal capsule; prolactin secreting tumors) increase the activity of tuberoinfundibular dopaminergic neurons. The activities of other dopaminergic neuronal systems are not affected by prolactin.

Animals↗
PubMed1982

Effects of chloral hydrate, gamma-butyrolactone, and equithesin on the efflux of dopamine and 5-hydroxytryptamine metabolites into cerebroventricular perfusates of rats.

Chloral hydrate, gamma-butyrolactone, and Equithesin are general anesthetics which have been employed in a variety of neurochemical and electrophysiological experiments. The effects of these anesthetics on the efflux of dopamine and 5-hydroxytryptamine metabolites into lateral cerebroventricular perfusates were determined in rats bearing chronically implanted cannulas. Chloral hydrate and Equithesin increased, whereas gamma-butyrolactone decreased, the efflux of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. None of the anesthetics had a consistent effect on the efflux of the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Changes in the rate of dopamine synthesis in the posterior pituitary during dehydration and rehydration: relationship to plasma sodium concentrations.

The rate of DOPA accumulation after the administration of a decarboxylase inhibitor (an in vivo estimate of dopamine synthesis) was determined in rat posterior pituitary, median eminence and striatum, regions containing terminals of tuberohypophyseal, tuberoinfundibular and nigrostriatal dopamine neurons, respectively. 3 days of water deprivation increased the hematocrit and the plasma sodium concentration and also increased the rate of DOPA accumulation in the posterior pituitary, but not in the striatum or median eminence. Water deprivation or substitution of 2% NaCl for drinking water for 5 days increased DOPA accumulation in the posterior pituitary and the plasma sodium concentration, while the hematocrit was increased only in the water-deprived group. Following 3 days of water deprivation, access to water for 3 h caused the elevated DOPA accumulation in the posterior pituitary and the plasma sodium concentration to return to control values while the hematocrit remained slightly elevated. Substitution of 2% NaCl for drinking water for 48 h to rats which had been water-deprived for 3 days restored the hematocrit to control, but did not alter the water deprivation induced increase in plasma sodium concentration or the rate of DOPA accumulation in the posterior pituitary. These results suggest that tuberohypophyseal dopaminergic neurons are regulated, at least in part, by sodium or osmoreceptors.

Animals↗
PubMed1982

Injection of hypertonic saline or mannitol accelerates the dehydration-induced activation of dopamine synthesis in the neurointermediate lobe of the rat hypophysis.

The rate of dopamine (DA) synthesis (DOPA accumulation after the administration of an inhibitor of aromatic L-amino acid decarboxylase) was determined in terminals of tuberohypophyseal DA neurons in the neurointermediate lobe (NIL) of the rat hypophysis at various times after the presentation of osmotic stimuli. DA synthesis in the NIL, but not in median eminence or striatum, was increased 24 h but not 4 h after an injection of hypertonic saline (5 ml 15% NaCl/kg, s.c.), provided the animals were not permitted access to water after the injection; 24 h of water deprivation per se was without effect on the rate of DA synthesis. DOPA accumulation in the NIL was also increased after an intravenous infusion of mannitol (25 ml 20% mannitol/kg) plus 24 h of water deprivation. These results suggest that the dehydration-induced activation of tuberohypophyseal DA neurons which is normally seen after 2-3 days of water deprivation can be accelerated if water deprivation is preceeded by injections of hypertonic saline or mannitol.

Animals↗
PubMed1981

Type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons in the rat.

Clorgyline (0.3-10 mg/kg, i.p.) inhibited type A monamine oxidase (5-hydroxytryptamine as substrate) but not type B monoamine oxidase (phenylethylamine as substrate) in homogenates of rat striatum and olfactory tubercle; deprenyl (0.3-3 mg/kg, i.p.) inhibited type B but not type A monoamine oxidase in these homogenates. The same doses of clorgyline increased concentrations of dopamine in striatum, and dopamine and norepinephrine in the olfactory tubercle, median eminence and posterior pituitary; they also reduced the concentrations of dihydroxyphenylacetic acid and the rate of synthesis of dopamine (DOPA accumulation after a decarboxylase inhibitor) in the same brain regions. On the other hand, the administration of deprenyl at doses that markedly inhibited type B monoamine oxidase did not alter the concentrations of dopamine, norepinephrine and dihydroxyphenylacetic acid or the rate of accumulation of DOPA in these brain regions. In addition, only clorgyline significantly lowered serum concentrations of prolactin. These results that type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal dopamine neurons.

Animals↗
PubMed1981

Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats.

The present study was designed to examine the role of 5-hydroxytryptamine (5-HT) neurons in the behavioral effects of d-lysergic acid diethylamide (LSD), an indolealkylamine hallucinogen, 2.5-dimethoxy-4-methylamphetamine (DOM) and mescaline, phenethylamine hallucinogens, and phenobarbital, a non-hallucinogen. Male rats, maintained at 70-80% of their free-feeding weights, were trained to press a lever for food pellet reinforcement on a fixed ratio-40 operant schedule. When trained, these rats responded at a constant, rapid rate (approximately 100 responses/min) during daily 40 min test sessions. Administration of hallucinogens caused an abrupt cessation of responding (a "pause"), for some portion of the session. The duration of this pause was dose-dependent for LSD (12.5-100 micrograms/kg), DOM (0.125-1.0 mg/kg) and mescaline (7.1-14.2 mg/kg). On the other hand, phenobarbital (12.5-50 mg/kg) did not cause pausing, but resulted in slowed, erratic intrasession response rates. When the same tests were repeated in rats that had previously received an intracerebroventricular injection of 5,7-dihydroxyptamine (5,7-DHT) the dose-response curves for the pausing induced by all three hallucinogens were shifted to the left, while the behavioral disruption produced by phenobarbital was unaltered. In these animals the 5-HT but not the norepinephrine concentrations was markedly reduced in all brain regions examined. These results suggest that 5-HT neurons are involved with the behavioral effects of hallucinogens but not of phenobarbital.

5,7-Dihydroxytryptamine↗
PubMed1981

The behavioral effects of hallucinogens in rats following 5,7-dihydroxytryptamine administration into the medial forebrain bundle.

The hypothesis that 5-hydroxytryptamine (5-HT) neurons and/or receptors are involved in the mechanism of action of hallucinogens is supported by the fact that intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) selectively destroys central 5-HT neurons in the brain and potentiates the behavioral effects of lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. The locus in the brain where this potentiation might occur is not known. In the present experiment, the medial forebrain bundle (MFB) was studied because it is the primary tract containing fibers from the cell bodies in the raphe nuclei to forebrain structures receiving 5-HT input. Male rats received 5,7-DHT (6 micrograms/2 microliter) or vehicle injections bilaterally into the MFB; this procedure caused a significant reduction of 5-HT in the cortex, hippocampus and hypothalamus of lesioned rats, but not in the striatum. Regional dopamine and norepinephrine concentrations were not affected by this treatment. The behavioral effects of the hallucinogens were tested in a situation in which the animals pressed a bar under a fixed ratio-40 (FR-40) schedule of food reinforcement. The disruptive effects of LSD on responding were enhanced in the 5,7-DHT-treated animals, while the effects of DOM were diminished; there was no change in the response to mescaline. These data suggest that, while 5-HT neurons are involved in the behavioral effects of hallucinogens, the precise sites and/or mechanisms of action of LSD, DOM and mescaline may differ.

5,7-Dihydroxytryptamine↗
PubMed1981

Dyskinesia: animal experimental correlates.

The results of behavioral studies in animals, which demonstrate increased effects of DA agonists after stopping chronic administration of neuroleptics, are consistent with an increased sensitivity of postsynaptic receptor and effector mechanisms in response to chronic disruption of DA transmission (disuse supersensitivity of DA receptors, see review by Moore & Thornburg (1975)). Although this mechanism may be responsible for the reversible withdrawal dyskinesias, it is probably not involved in persistent tardive dyskinesia. The persistence of the latter dyskinesias suggests an irreversible structural or chemical change, but with the exception of a report by Christensen et al. (1970) there is little evidence of neuroleptic-induced degenerative changes in the brains of man or animals. Although the etiology of tardive dyskinesias remains a mystery, pharmacological evidence suggests a functional overactivity of extrapyramidal mechanisms mediated by DA. To date, however, experiments with animal models have not provided a logical explanation for this overactivity.

Animals↗
PubMed1981

Biochemical indices of catecholaminergic neuronal activity in the median eminence during the estrous cycle of the rat.

An attempt was made to correlate the changes in blood concentrations of prolactin and luteinizing hormone (LH) which occur during the estrous cycle of rats with changes in biochemical estimates of the activities of dopamine (DA)- and norepinephrine (NE)-containing neurons in the median eminence. The serum concentrations of prolactin and LH markedly increased on the afternoon and evening (16.00-24.00 h) of proestrus. The steady state concentrations of NE and DA in the median eminence did not change at any time during the estrous cycle, but the alpha-methyltyrosine-induced decline of NE was increased during the morning of proestrus (8.00-12.00 h) while the decline of DA was decreased (12.00 h). The rate of total catecholamine synthesis (Dopa accumulation after a decarboxylase inhibitor) in the median eminence was not markedly altered at any time during the estrous cycle; the lack of change of dopa accumulation on proestrus may be due, in part, to opposing changes in the rates of amine synthesis in Ne and Da neurons.

Animals↗