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Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1994

Nuclear DNA introgression across a Pyrenean hybrid zone between parapatric subspecies of the grasshopper Chorthippus parallelus.

Two parapatric subspecies of the European grasshopper Chorthippus parallelus meet along the Pyrenees and form a hybrid zone. A nuclear DNA sequence marker (cpnl-1), involving the presence or absence of a 5 bp insertion, was found to differentiate between the two subspecies along either side of the High Pyrenees but further electrophoretic and sequence analyses revealed that considerable mixing of the subspecific genomes had occurred towards the western and eastern ends of the Pyrenees. The cline for this marker was relatively narrow in two adjoining western central high cols (Peyrelue: 9.7 km and Portalet: 13.3 km) but was significantly wider in another central high col towards the east (Quillane: 42.3 km), indicating that a different combination of forces has been operating on this locus in different regions of the Pyrenees.

Animals↗
PubMed1993

Evolution and expression of a beta-like globin gene of the Australian marsupial Sminthopsis crassicaudata.

A beta-like globin gene was isolated from the Australian dasyurid marsupial Sminthopsis crassicaudata. Nucleotide-sequence analysis of promoter and coding regions of the gene revealed that it was orthologous to eutherian early-expressed (epsilon, gamma, eta) beta-like globin genes. Comparison of the conceptually translated sequence of the gene with a partial amino acid sequence of the adult beta-globin chain from S. crassicaudata provided evidence that the gene was not expressed in adult tissues. In addition, Northern analysis of RNA isolated from an embryo, pouch young, and adult bone marrow indicated that the gene was expressed predominantly in embryonic tissues and that there was a significant reduction in the expression of the gene within a day of birth. These results provide strong support for the hypothesis of Koop and Goodman [Koop, B. F. & Goodman, M. (1988) Proc. Natl. Acad. Sci. USA 85, 3893-3897] that an embryonic beta-like globin gene existed prior to the divergence of the eutherian and marsupial lineages and that this gene was already differentiated with respect to its promoter regions and developmental expression. The observation that epsilon-globin mRNA was present at least until day 4 postpartum suggests that the epsilon-globin chain may play some role in influencing the physiological properties of hemoglobin in S. crassicaudata neonates.

Aging↗
PubMed1993

The benzodiazepine receptor partial agonist bretazenil and the partial inverse agonist Ro 15-4513: effects on salt preference and aversion in the rat.

The general aim of the present series of experiments was to contrast the effects of the benzodiazepine receptor (BZR) partial agonist bretazenil and those of the partial inverse agonist Ro 15-4513 in two-choice tests between saline (0.9% or 1.8%) and water, using water-deprived rats. Since BZR agonists appear to enhance positive hedonic reactions to taste stimuli selectively, it was hypothesized that bretazenil (and a second BZR partial agonist Ro 17-1812) would selectively enhance intake of a preferred 0.9% salt solution, but not necessarily reduce the relative aversion to a more concentrated 1.8% salt solution, in these choice tests. The results were in general agreement with these hypotheses. Despite an earlier finding that Ro 15-4513 abolished sweet taste preference, there was no evidence here that it reduced the relative preference expressed for 0.9% NaCl solution. Moreover, Ro 15-4513 did not enhance the relative avoidance of the 1.8% NaCl solution. The BZR antagonist, flumazenil, had no effect on either salt preference or aversion. These results indicate that the type of taste stimulus (sweet or salt), the type of behavioural response (preference or aversion) and the type of BZR ligand (agonist, antagonist or inverse agonist) interact to determine the observed behavioural consequences in choice tests.

Animals↗
PubMed1993

Cocaine: a microstructural analysis of its effects on feeding and associated behaviour in the rat.

Cocaine (5.6-30 mg/kg, i.p.) was administered to nondeprived male rats trained to eat a palatable sweetened mash. Over a 60-min period, their behaviour was observed and recorded for a microstructural analysis. Cocaine suppressed feeding in a dose-dependent manner (significantly at 10 mg/kg and greater), and this was due in the main to a reduction in the frequency of eating bouts. In contrast, the mean duration of eating bouts was unaffected, except at the highest dose, 30 mg/kg. In addition, the rate of eating was not significantly affected by cocaine at any dose. Time-course data revealed that cocaine, at anorectic doses (10-30 mg/kg), initially suppressed feeding completely, and the duration of this suppression was proportional to the dose. In effect, cocaine delayed the initiation of feeding, thus bringing about the reduction in the number of eating bouts. Cocaine caused some stimulation of locomotor activity and rearing to the side of the observation tank, but did not affect rearing away from the centre, or immobility. Grooming proved to be very sensitive to cocaine's suppressant effect, with substantial inhibition occurring at 5.6 mg/kg (a sub-anorectic dose). These data are compared with previously published work with D-amphetamine and are contrasted with results for selective D1 and D2 dopamine receptor agonists.

Animals↗
PubMed1993

Fetal dopamine cell survival after transplantation is dramatically improved at a critical donor gestational age in nonhuman primates.

Mesencephalic tissue containing newly generated dopamine neurons was collected from brains of embryonic African green monkeys at 44 and 49 days of gestation and stereotaxically implanted into multiple sites in the caudate nucleus of adult monkeys previously treated with the dopamine protoxin, 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine. Ultrasonography was utilized to assess the developmental stage prior to hysterotomy. Brains were removed for combined histochemical and biochemical analyses at 3 1/2 months after grafting to determine the extent of graft survival and growth. The dopamine content of the target nucleus was assessed from microdissected "punches" placed in proximity to grafts identified in unfixed brain slices prior to fixation. Tissue dopamine levels adjacent to the grafts were elevated markedly, reaching 25-50% of control levels at some sites in the caudate nucleus. Morphometric analysis of graft size and dopamine cell numbers was performed with computer-enhanced, video-based imaging. Exceptionally large grafts that far exceeded their initial size at the time of implantation were seen at each placement site. The dopamine cell count was as high as 3500 in a single graft from E44 tissue, but only as high as 550 from the E49 donor. Up to 15,000 tyrosine hydroxylase-positive neurons were stained in the host monkey that received E44 tissue; only 1/10 as many were seen in each of the recipients of E49 day samples. The earlier donor grafts occupied as much as 15% of the caudate nucleus as seen in a single coronal section; summation of all sections that contained grafts at each placement from the E44 donor revealed average areas occupied by the grafts ranging from 3 to 8% of the caudate nucleus. In comparison, grafts produced from an E49 donor averaged between 2.4 and 5.4% of the area of the target. Qualitatively, grafts from each gestational stage showed well-developed dopamine neurons with morphological characteristics equivalent to those of all three ventral mesencephalic dopamine cell groups. The attainment of large, well-differentiated grafts with thousands of dopaminergic neurons from early gestation tissue suggests that optimal cell survival in primates is dependent on the degree of postgerminal development of the dopamine neuron. Neurite extension may be critical in this regard as well as other, at present, undefined factors. Maximal graft development and cell survival may be a critical element in the ability of neural grafts to reverse a neurological disability and to maintain improvement in the event of continued degeneration of host dopamine neurons.

Animals↗
PubMed1993

Selective dopamine D-1 receptor agonists, SK&F 38393 and CY 208-243 reduce sucrose sham-feeding in the rat.

Gastric-fistulated rats were trained to sham-feed a 10% sucrose solution in a 60 min test. The selective dopamine D-1 receptor agonists, SK&F 38393 (3 and 10 mg/kg, s.c.) and CY 208-243 (1 and 3 mg/kg, s.c.) both produced dose-related reductions in sham-feeding. These effects were present in the first 5 min of the test period, and persisted throughout the remainder of the test. The data confirm and extend results for an anorectic effect of SK&F 38393 and demonstrate, for the first time, a similar anorectic effect of CY 208-243.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

A microstructural analysis of the effects of presatiation on feeding behavior in the rat.

Rats were familiarized with eating a sweetened mash, and were divided into three groups. Before a test meal, the animals were allowed to eat the mash for 0, 2.5, or 5 min, respectively, to vary the degree of their satiation. Their subsequent consumption of the meal and their behavior over the course of a 30-min period was observed, to provide a microstructural description of the behavioral changes that are characteristic of increasing satiation. Presatiation, as expected, reduced the size of the test meal, and did so predominantly by reducing the duration of feeding, especially during the first 5 min of the test period. There was a slight reduction in the rate of eating as a function of presatiation, and a tendency for the latency to initiate feeding to increase. When other responses were considered separately, there was little effect of presatiation on their microstructural parameters. However, the duration of a composite category (comprising rearing, grooming, and stationary) did increase significantly as a function of presatiation. These data provide a behavioral template for satiation, against which to compare treatments that purport to manipulate feeding satiation.

Animals↗
PubMed1993

Effects of selective 5-HT1 receptor agonists in water-deprived rats on salt intake in two-choice tests.

Twenty-two-hour water-deprived rats were divided into two groups: The first was given access to 1.8% saline and water in a 30-min two-choice test; the second was given access to 0.9% saline and water in the same type of intake preference test. Animals were tested following administration of several selective 5-hydroxytryptamine1 (5-HT1) receptor agonists. The results indicated a clear-cut distinction between the effects of selective 5-HT1A receptor agonists, on the one hand, and putative 5-HT1B/1C agonists on the other. Ipsapirone, gepirone, and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all showed evidence of increasing the consumption of 1.8% saline (less preferred to water) but had no effect on intake of the more preferred 0.9% saline. In contrast, 1-3-(chlorophenyl)piperazine (mCPP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) (5-HT1B/1C agonists) reduced intake of 1.8 and 0.9% saline in the two tests. One interpretation of these results is to assume that the 5-HT1A agonists act at inhibitory autoreceptors to diminish central serotonergic activity, while mCPP and TFMPP act postsynaptically to enhance serotonergic activity. The possibility is discussed that mCPP and TFMPP may act to increase the perceived salt concentration during drinking, whereas the 5-HT1A agonists may have the opposite effect.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

The selective 5-HT3 receptor antagonist, ondansetron, augments the anorectic effect of d-amphetamine in nondeprived rats.

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-HT3) receptor antagonists either block or have no effect on amphetamine-induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affect the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Nondeprived male rats were tested in two feeding paradigms: consumption of a palatable sweetened mash and ingestion of a 3% sucrose solution. Ondansetron (10-100 micrograms/kg) did not antagonize amphetamine-induced anorexia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but the direction of the effect differed according to the paradigm. Sweetened mash intake was significantly increased at 30 and 100 micrograms/kg, while sucrose ingestion was significantly reduced at 10 and 30 micrograms/kg ondansetron. It is suggested that ondansetron has two opposing effects on intake, one of which (hyperphagia) can be masked by d-amphetamine, leaving an anorectic effect that augments that of d-amphetamine.

Animal Feed↗
PubMed1993

Effects of d-fenfluramine, MK-212, and ondansetron on saline drinking in two-choice tests in the rehydrating rat.

The aim of the present studies was to investigate the effects of serotonergic compounds on preference for isotonic saline and aversion to hypertonic saline, respectively. Twenty-two-hour water-deprived rats were divided into two groups: The first was given a choice between 0.9% saline and water in a 30-min test; the second was given a choice between 1.8% saline and water. Animals were tested following administration of d-fenfluramine, the 5-HT1C receptor agonist 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), and the 5-HT3 receptor antagonist ondansetron. d-Fenfluramine (0.3-3.0 mg/kg) did not reduce 0.9% saline preference; instead, at 0.3 mg/kg there was a significant increase in saline drinking. In contrast, MK-212 (0.3-3.0 mg/kg) abolished the preference for isotonic saline whereas ondansetron (10-100 micrograms/kg) had no effect. d-Fenfluramine and MK-212 reduced hypertonic saline drinking, although at the highest dose for each drug water drinking was also reduced. These data add further to the evidence for an important serotonergic involvement in the control of saline drinking and preference in the rat.

Animals↗
PubMed1993

Nuclear DNA sequence divergence between parapatric subspecies of the grasshopper Chorthippus parallelus.

Sequence data from a non-coding nuclear DNA segment (Cpnl-1) was used to investigate the divergence between Spanish and French subspecies of the grasshopper Chorthippus parallus which form a hybrid zone in the Pyrenees. The spatial distribution of eighteen Cpnl-1 sequence haplotypes from eighteen French and fifteen Spanish populations and phylogenetic analyses using both distance and parsimony procedures provide strong evidence that the Pyrenean hybrid zone was formed by postglacial secondary contact and that the French subspecies arose by range expansion from a Balkan or Italian refugium. In addition, the data provide evidence for subdivision between grasshoppers from Northern Spain and those from Central and Pyrenean Spanish populations.

Animals↗
PubMed1992

The beta-carboline abecarnil, a novel agonist at central benzodiazepine receptors, influences saccharin and salt taste preferences in the rat.

Abecarnil is a recently described beta-carboline which acts at central benzodiazepine receptors (BZR) and has anxioselective/anticonvulsant properties. While it may be classified provisionally as a partial agonist at BZR, there is also evidence that its pharmacological profile may be due to a selective action at BZR subtypes. The general aim of the present series of experiments was to investigate the effects of abecarnil on ingestional behaviour in the rat. The results indicated that abecarnil (0.3-10 mg/kg, i.p.) selectively increased the intake of preferred 0.05% sodium saccharin and 0.9% sodium chloride solutions in two-choice tests using water-deprived rats. These results confirm and extend previous work with the potent BZR agonist clonazepam. Moreover, abecarnil significantly increased the ingestion of sweetened mash and 3% sucrose solution in nondeprived animals. In general, these results indicate that abecarnil is effective in increasing ingestional responses, a characteristic it shares with classical agonists like diazepam. The results could be accounted for in terms of a partial agonist profile for abecarnil, but do not rule out the possibility of selective actions at BZR subtypes.

Animals↗
PubMed1992

5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia.

Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) are associated with suicidal behaviour in patients with depressive illness, but studies of the relation between CSF 5-HIAA and suicide in schizophrenia have been inconclusive and have not included long-term follow-up. In a prospective study, we measured 5-HIAA in CSF taken from 30 schizophrenic patients in a drug-free state, and followed these patients for 11 years. 10 patients made suicide attempts during follow-up. Suicide attempters had significantly lower concentrations of CSF 5-HIAA at initial evaluation than non-attempters (mean [SE] 6.7 [2.2] vs 23.6 [5.6] ng/ml, p < 0.05). Our findings provide further evidence of the relation between serotoninergic dysfunction and suicide, and suggest a role for drugs with serotoninergic effects in schizophrenia.

Female↗
PubMed1992

A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia.

Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D2)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150-300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P = 0.015). Efficacy analyses using clinical global impression (P = 0.04) and change in BPRS scores (P = 0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.

Adult↗
PubMed1992

Behavioural pharmacology of 5-HT3 receptor ligands.

Extensive studies have ascribed a role for the central 5-HT3 receptor in the modulation of behaviour. Much of the work stems from the actions of potent and selective 5-HT3 receptor antagonists; these agents reduce mesolimbic dopamine initiated hyperactivity, release suppressed behaviour, reduce the reinforcing properties and withdrawal symptoms of drugs of abuse, enhance cognitive performance and modulate appetite. This article reviews the preclinical and clinical evidence implicating the 5-HT3 receptor in these indications and discusses the potential neurochemical mechanisms underlying the behavioural changes.

Animals↗
PubMed1992

CCK antagonists and CCK-monoamine interactions in the control of satiety.

The introduction of potent cholecystokinin (CCK) receptor antagonists, selective for either the CCK-A or the CCK-B subtype, has provided a great impetus to the study of activity of endogenous CCK in relation to the control of feeding. This paper reviews experiments in which devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B-gastrin receptor antagonist) have been used. Both compounds increase food consumption (under certain conditions) and postpone the onset of satiety. L-365,260 is the more potent, suggesting a role for central CCK-B type receptors in satiety. In addition, use of CCK antagonists permits the study of important functional interactions between CCK and other neurochemical factors that serve to control feeding. Thus, devazepide, but not L-365,260, blocked the anorectic effect of either d-fenfluramine or serotonin. Hence, CCK-A type receptors appear to be involved in the anorectic effect of these drugs. This result serves as an example to illustrate a principle of cooperativity in the satiety-inducing effects of diverse neurochemical signals.

Animals↗
PubMed1992

Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic.

"The birth dates of schizophrenic inpatients in eight health regions in England and Wales were reviewed for any effect of the 1957 A2 influenza epidemic. 5 months after the peak infection prevalence, the number of births of individuals who later developed schizophrenia was 88% higher than the average number of such births in the corresponding periods of the 2 previous and the next 2 years. This finding is in accordance with a study from Helsinki and with clinical and neuropathological evidence of aberrant fetal brain development in the pathogenesis of schizophrenia."

Disease Outbreaks↗