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Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 127 records · Page 7Linked to original sources
PubMed1988

Naloxone attenuation of sham feeding is modified by manipulation of sucrose concentration.

The time course of sucrose (5, 10 and 20%; w/v) sham feeding was monitored in one hour tests. Intake levels increased as a function of concentration. Naloxone (1.25 mg/kg, IP) attenuated the sham feeding of 10% sucrose solution in gastric fistulated rats, without affecting initial intake rates. Furthermore, after naloxone the intake pattern of 10% sucrose was identical to that for 5% sucrose in untreated rats. In a second test, substitution of 10% sucrose by a 20% solution after 15 min of sham feeding reversed the effect of naloxone, restoring intake to 10% baseline levels. Thus naloxone's effect appeared to be behaviourally equivalent to that of sucrose dilution and was counteracted by increasing sucrose concentration. Naloxone was apparently more effective against the lower sucrose concentration, suppressing intake at an earlier stage of testing. The data confirm the importance of oropharyngeal stimulation to the suppressive action of naloxone and support opioid mediation of orosensory reward.

Animals↗
PubMed1988

Profile of the selective dopamine D-2 receptor agonist N-0437: its effects on palatability- and deprivation-induced feeding, and operant responding for food.

N-0437 is a potent and highly selective dopamine D-2 receptor agonist, which has been used in the present series of experiments to investigate its potential anorectic properties. In doses of 0.3-3.0 mg/kg (IP), N-0437 significantly reduced consumption of a sweetened palatable mash in nondeprived mice (minimal effective dose, 0.3 mg/kg) and rats (minimal effective dose, 0.56 mg/kg). Reduction in food intake were also produced in rats by the less potent, but selective, D-2 agonist RU 24213 (effective at 10.0 mg/kg), and by d-amphetamine (1.0 and 3.0 mg/kg). The anorectic effect of N-0437 (1.0 mg/kg) was completely antagonized by the selective D-2 antagonist, YM-09151-2 (0.01 mg/kg). Over a series of 10 injections, N-0437 (1.0 mg/kg) maintained its effect to reduce palatable food intake. In food-deprived rats, N-0437 (0.3-3.0 mg/kg, IP) also reduced consumption of standard laboratory food, and dose-dependently reduced operant responding for food under a FR8 schedule of reinforcement. The results of the experiments are discussed in terms of a possible direct effect to reduce feeding responses resulting from stimulation of postsynaptic dopamine D-2 receptors.

Animals↗
PubMed1988

Attenuation of sham feeding by naloxone is stereospecific: evidence for opioid mediation of orosensory reward.

The time course of the suppressive action of naloxone on sham feeding was examined in gastric fistulated rats. One hour sham intake of 30% sucrose solution was halved by 1.25 mg/kg IP (-)-naloxone. A maximal 75% reduction was obtained with 2.5 mg/kg. Naloxone's effect appeared to mimic the attenuation of intake rate produced by sucrose dilution. The stereoisomer (+)-naloxone (1.25, 2.5 and 10 mg/kg IP) was ineffective. These data confirm the involvement of opioid receptors in naloxone anorexia and are consistent with opioid involvement in the rewarding aspects of ingestion.

Animals↗
PubMed1988

Expression of a 150-kD cell surface antigen identified by monoclonal antibody YB5.B8 is associated with poor prognosis in acute non-lymphoblastic leukaemia.

Peripheral blood specimens, obtained from 71 patients with newly-diagnosed acute non-lymphoblastic leukaemia (ANLL) prior to the initiation of therapy, were assayed for the presence of a myeloid leukaemia-associated cell surface antigen identified by monoclonal antibody YB5.B8. The antibody bound to cells from 22 patients, and these patients had a poorer overall survival rate than those whose cells failed to bind the antibody (p less than 0.025). Fifty patients were treated with daunorubicin/cytosine arabinoside/6-thioguanine (DAT) according to a standard protocol and survived at least to the end of the induction phase (7 days). Of the 34 patients whose cells were YB5.B8 negative, 28 obtained a complete remission. In contrast, only four of the 16 patients whose cells expressed YB5.B8 antigen obtained complete remission (p less than 0.001). Expression of the YB5.B8 antigen in ANLL appears to be a strong prognostic indicator which is independent of other known prognostic factors such as patient age, leucocyte count and pre-existing hematopoietic abnormality.

Adolescent↗
PubMed1988

The effect of electroconvulsive therapy on CSF amine metabolites in schizophrenic patients.

The effects of a series of six ECT treatments were observed on the CSF concentrations of HVA, MHPG, and 5-HIAA in 12 patients suffering from schizophrenia. Four patients were previously neuroleptic drug-free, and eight had received only oral neuroleptic drugs at the same dose for more than 4 weeks. A significant increase in the concentration of HVA was observed after the first ECT treatment but not after the final treatment. No significant changes were observed in the concentrations of MHPG and 5-HIAA. The patients improved clinically, and the results suggest that ECT has important effects on dopaminergic systems.

Adult↗
PubMed1988

Human myeloid differentiation antigens identified by monoclonal antibodies to the myelomonocytic leukemia cell line RC-2A.

Murine monoclonal antibodies to human myeloid cell surface differentiation antigens were prepared using the myelomonocytic leukemia cell line RC-2A as immunogen. Using a highly sensitive colorimetric assay, antibodies were selected as myeloid-associated based on their binding to RC-2A cells, but not to cells of the autologous EBV-transformed* B cell line Cess-B. Antibodies to five distinct cell surface antigens were extensively characterized for their binding to normal and leukemic hemopoietic cells, and to tissue sections. Three antibodies may identify antigens previously described in the International Leucocyte Typing Workshops (CD14, CD11b and CD31). The other two antigens appear to be expressed at low levels on the surface of RC-2A cells, and do not correspond to existing CD groups. One of these is also present on monocytes and neutrophils. Both were present on myeloid progenitor cells, as judged by depletion experiments with antibody and complement, although neither bound appreciably to myeloid leukemic cells as judged by indirect immunofluorescence. The other three antibodies bound preferentially to leukemic specimens displaying monocytic differentiation. Four of the antibodies could be demonstrated to bind to cells in frozen sections of tonsil and small intestine and all gave distinct patterns of reactivity. In particular, these antibodies differed markedly in their binding to endothelium, follicular dendritic cells and various types of tissue macrophages. These antibodies may be useful in the study of the differentiation of myeloid cells and in studies of immunologically mediated disease such as allograft rejection.

Animals↗
PubMed1987

CGS 8216 treatment decreases central-type benzodiazepine receptors in rat brain.

Central- and peripheral-type benzodiazepine receptors were analyzed in several brain areas of rats (n = 8-9) that had been treated for five days with CGS 8216 (20 mg/kg per day). Twenty-four hours after cessation of drug treatment a significant decrease of central-type benzodiazepine receptors as labeled by [3H]beta-carboline-3-carboxylate ethyl ester ([3H]beta CCE) and [3H]flunitrazepam ([3H]FNZ), but not of peripheral-type benzodiazepine receptors as labeled by [3H]RO 5-4864 could be observed in the animals treated with CGS 8216.

Animals↗
PubMed1987

Requirements for the stimulation of allogeneic T lymphocytes by acute non-lymphoblastic leukaemia cells.

Blast cell populations from 32 patients with acute non-lymphoblastic leukaemia of various morphological types have been examined for their ability to stimulate allogeneic T lymphocytes from normal donors in one-way mixed leucocyte culture (MLC). At the same time, these leukaemic cell populations were examined for the amounts of major histocompatibility complex Class I and Class II antigens they expressed, and their ability to release interleukin 1 (IL1) in culture both with and without stimulation by lipopolysaccharide. The abilities of the leukaemic cell populations to stimulate in MLC, and to produce IL1, were found to be associated with the expression of morphological characteristics of monocytic differentiation, and correlated significantly. In contrast, no correlation was observed between the extent of Class I or Class II expression and MLC stimulatory ability. Many myeloblast populations of immature phenotype were unable to stimulate allogeneic T cells despite their strong expression of these antigens. This lack of stimulatory ability was not overcome by the addition of exogenous IL1. We therefore conclude that the correlation between the production of IL1 and MLC stimulatory ability does not necessarily imply a cause/effect relationship, and that the interaction between allo-antigen and the T cell receptor together with a supply of lymphokine 'co-stimulator' is not sufficient to activate resting T lymphocytes. The failure of some Class I and II antigen positive leukaemic blasts to stimulate in MLC even in the presence of exogenous IL1 may be due to the lack of other differentiation-associated cell surface molecules necessary for stable cell-cell interaction.

Antigens, Neoplasm↗
PubMed1987

Adrenalectomy and the anorectic effects of benzodiazepine inverse agonists and opiate antagonists in rats fed a palatable diet.

The benzodiazepine (BZ) receptor inverse agonists, FG 7142 (1.25-10.0 mg/kg, IP) and CGS 8216 (2.5-20.0 mg/kg, IP), significantly attenuated the consumption of a palatable sweetened diet by non-deprived male rats in a 30 min test. Adrenalectomy failed to affect the reduction in food intake produced by these two drugs. Similarly, the anorectic effects of the opiate antagonists, naltrexone (0.3-3.0 mg/kg, SC) and diprenorphine (0.3-3.0 mg/kg, SC) in the same feeding paradigm were unaffected by adrenalectomy. So far as palatability-induced feeding in concerned, anorectic effects of BZ inverse agonists and opiate-antagonists appear to be adrenal-independent in the rat. The benzodiazepines, clonazepam (0.3 mg/kg, IP) and diazepam (1.0 mg/kg, IP), stimulated food consumption in both adrenalectomized and sham-operated animals.

Adrenal Glands↗
PubMed1987

Chlordiazepoxide-induced selection of saccharin-flavoured food in the food-deprived rat.

Following a period of food-deprivation, adult male rats were given a choice between three sources of food in a 15 min test. All three consisted of a mash of powdered food and water; saccharin and quinine were added to two of them, respectively. Chlordiazepoxide (5 and 10 mg/kg, IP) significantly reduced the latency to begin eating, and also increased the overall level of food consumption. Its hyperphagic effect was due to a selective increase in ingestion of the saccharin-flavoured food, and was not due to a general increase in food consumption across all three food sources. Analysis of the micro-structure of feeding indicated that the increase in food intake depended upon an increase in the duration of individual bouts. Other feeding parameters were not significantly affected by chlordiazepoxide. These data suggest the CDP treatments affect feeding behaviour selectively, both in relation to the taste characteristics of the food, and also with regard to alterations in the micro-structure of the feeding responses.

Animals↗
PubMed1987

Partial agonists acting at benzodiazepine receptors can be differentiated in tests of ingestional behaviour.

Several categories of compounds active at benzodiazepine receptors (BZR) in the brain have been distinguished: agonists, antagonists and the novel category of inverse agonist. In terms of their effects on ingestional responses (e.g., food, saline and water consumption), agonists increase levels of intake, inverse agonists reduce intake in some, if not all, tests, while antagonists block the effects of both agonists and inverse agonists. Attention is currently focussed upon a range of compounds which fall between full agonists and antagonists. These partial agonists are of particular interest since they act more selectively than full agonists, retaining effects in animal models of anxiolytic and anticonvulsant activity, for example, while largely lacking behaviourally-depressant effects. Recent data indicate that tests of ingestional behaviour distinguish between various BZR partial agonists. The benzodiazepines Ro23-0364, Ro16-6028 and Ro17-1812, as well as the beta-carboline ZK 91296, enhanced ingestional responses. The pyrazoloquinolines, CGS 9895 and CGS 9896, did not, but antagonized agonist-induced increases in ingestion.

Animals↗
PubMed1987

Differential effects of benzodiazepine receptor ligands on isotonic saline and water consumption in water-deprived rats.

Water-deprived male rats were adapted to a 30 min test of water or saline drinking in a single-bottle acceptance test. The potent benzodiazepine agonist, clonazepam, produced significant increases in both water and saline consumption. Increases in the consumption of both were also obtained with the non-benzodiazepine agonist, zopiclone (a cyclopyrrolone), but not with the pyrazoloquinoline agonist, CGS 9896. Hence, some, but not all, benzodiazepine receptor agonists enhance drinking responses. The benzodiazepine receptor antagonists, Ro15-1788 and CGS 8216, had no significant effect on the intake of either isotonic saline or water. In contrast, the beta-carboline FG 7142, which has been described as an inverse agonist acting at benzodiazepine receptors, reduced both saline and water drinking at 10 and 20 mg/kg. Although the baseline level of saline drinking was considerably higher than that of water, there was no general indication that any drug effect on consumption interacted with the type of fluid in the drinking test. However, in the case of agonist-induced increases in consumption, peak effects occurred at different doses; they were lower for saline- than for water-drinking.

Animals↗
PubMed1987

The pyrazoloquinoline, CGS 8216, reduces sham feeding in the rat.

The pyrazoloquinoline CGS 8216, a benzodiazepine receptor ligand, produced a dose-related (2.5-10.0 mg/kg, IP) attenuation of sham feeding a 30% sucrose solution by rats with open gastric fistulas. Ingestion was reduced by over 50% following the largest dose of CGS 8216 in a 60 min test. The initiation of sham feeding was not delayed by CGS 8216, but sham feeding was subsequently slowed over an extended test period. The suppressant effect of CGS 8216 was reversed by the specific benzodiazepine receptor antagonist Ro15-1788 (20 and 40 mg/kg, IP). Hence the effect of CGS 8216 on sham feeding may be mediated by benzodiazepine receptors, and is consistent therefore with the characterization of CGS 8216 as a benzodiazepine partial inverse agonist. In contrast to sham feeding, CGS 8216 (10.0 mg/kg, IP) did not affect sham drinking in 17 hr water-deprived rats. The results are discussed in relation to possible benzodiazepine receptor involvement in the neurochemical mediation of food palatability.

Animals↗
PubMed1987

Benzodiazepines and putative 5-HT1A agonists increase hypertonic saline consumption in rehydrating rats.

Male rats were adapted to a 22 hr water-deprivation schedule, and to a 30 min test of hypertonic (1.8 or 2.7%) NaCl solution ingestion. A novel benzodiazepine, Ro23-0364, recently reported to have anxiolytic activity in rats and squirrel monkeys but to have limited potential to produce unwanted side effects, produced significant dose-related increases in hypertonic saline ingestion. Midazolam, a benzodiazepine full agonist, increased salt intake but the effect was offset at higher doses by the induction of sedation. Three putative 5-HT1A agonists, proposed as nonbenzodiazepine-related anxiolytics, were also tested: the highly selective 8-OH-DPAT, gepirone and ipsapirone (TVX Q 7821). In each case, occasions when hypertonic saline consumption was significantly increased were detected. At 300 micrograms/kg of 8-OH-DPAT and 10 mg/kg of gepirone, the appearance of a pronounced flattened body posture effectively interfered with drinking responses. It appears possible that a behavioural action shared by benzodiazepines and 5-HT1A agonists may be responsible for the increased hypertonic saline ingestion.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Novel benzodiazepine receptor ligands stimulate intake of hypertonic NaCl solution in rehydrating rats.

Experiments were conducted to determine the degree of generality of previous findings that anxiolytics increased the ingestion of hypertonic saline in rehydrating rats. Further, potential differential effects amongst recently described benzodiazepine receptor partial agonists were explored. Finally, the hypothesis that benzodiazepine receptor partial inverse agonists would decrease the ingestion of hypertonic NaCl solution was tested. Results indicated that full agonists (midazolam, ZK 93423, zopiclone) produced substantial dose-related increases in hypertonic saline consumption. The putative 5-HT1A agonist, buspirone, produced only a dose-dependent decrease in saline intake. Partial agonists fell into two distinct categories: ZK 91296, CL 218,872 and two novel benzodiazepines, Ro16-6028 and Ro17-1812, also increased saline ingestion. In contrast, two pyrazoloquinolines, CGS 9896 and CGS 9895, had no significant effect on intake. Two compounds, CGS 8216 and FG 7142, described as benzodiazepine partial inverse agonists, did not significantly affect consumption of the hypertonic saline.

Animals↗
PubMed1987

The benzodiazepine partial agonists, Ro16-6028 and Ro17-1812, increase palatable food consumption in nondeprived rats.

Two novel imidazobenzodiazepines, Ro16-6028 and Ro17-1812, have been described recently as partial agonists acting at benzodiazepine receptors. In a test of palatable food consumption using nondeprived rats, Ro16-6028 (0.01-10 mg/kg) and Ro17-1812 (0.01-10 mg/kg) were shown to produce dose-dependent increases in food intake. Ro16-6028 was more potent than Ro17-1812. Suriclone, midazolam, and the beta-carbolines ZK 93423 and ZK 91296 also significantly increased food intake. The maximum effects of Ro16-6028 and Ro17-1812 were at least equivalent to those obtained with full agonists acting at benzodiazepine sites. Neither Ro16-6028 nor Ro17-1812 reduced locomotion or rearing frequency in an open field test, although there was a reduction in grooming frequency. In contrast, the full agonist midazolam dose-dependently reduced all measures of general activity. The results indicate that some novel benzodiazepine partial agonists strongly stimulate food intake in the absence of side effects typical of the classical benzodiazepines.

Animals↗