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R J Rodgers

Publications and source records attributed to R J Rodgers.

At least 91 records · Page 5Linked to original sources
PubMed1996

Comparing different forms of male and female aggression in wild and laboratory mice: an ethopharmacological study.

The purpose of this study was to compare the effects of 2 mg/kg fluprazine (a serotonergic psychoactive drug with antiaggressive properties) on intrasexual attack, infanticide, and predation (on an insect larva) in males and females of wild and Swiss mice. The results showed that, in both stocks of mice, fluprazine significantly inhibited intrasexual and infanticidal attack in both sexes, but predatory attack was not altered by the drug treatment. Motivational and neural substrates underlying intrasexual attack and infanticide appear, thus, to be related to each other, and similarly modulated in both males and females. Conversely, predatory attack seems to be under a different neurohumoral control. The similar regulation of proximal mechanisms of aggressive behavior observed in wild and Swiss mice suggests a common neurobiology of aggression. For this reason, the outbred laboratory Swiss mice appear to be a reliable model for studies on causal and functional mechanisms of aggression.

Aggression↗
PubMed1996

Production of extracellular matrix, fibronectin and steroidogenic enzymes, and growth of bovine granulosa cells in anchorage-independent culture.

A proportion of the granulosa cells from bovine antral follicles will survive, like stem cells, in anchorage-independent culture. To study these cells, bovine granulosa cells were isolated from medium-sized follicles (3-5 mm), plated out (in aliquots of 2.5 x 10(4) viable cells) onto a 1 mL agar base, and overlaid with 1 mL of methycellulose solution in culture medium (control). The cells were cultured (14 days) and then processed for histology (n = 14) or Western immunoblotting (n = 5). Under control conditions or after treatment with basic fibroblast growth factor (bFGF; 50 ng mL-1), a proportion of the granulosa cells divided to produce colonies; individual cells remained small. bFGF increased the number of cells harvested (15.8 +/- 7.3-fold, as measured indirectly by the relative amount of the nuclear La antigen), increased the average diameter of the colonies from 88.9 +/- 13.5 microns to 136.5 +/- 4.9 microns and stimulated the production of fibronectin 5.7 +/- 1.5-fold (P < 0.05). An extracellular matrix, which has previously been shown to be a basal lamina, was observed in 19.1% of the colonies (total of 350 colonies examined; n = 8 experiments). Cells treated with dibutyryl cAMP (1 mM) hypertrophied and had 50 +/- 28.7-fold and 102.6 +/- 55.8-fold higher levels of cholesterol side-chain cleavage cytochrome P450 (P < 0.001) and 3 beta-hydroxysteroid dehydrogenase (P < 0.01) respectively (n = 5). Thus, granulosa cells with characteristics of stem cells can divide and produce extracellular matrix, or be induced to differentiate when in culture without anchorage.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Morphological characterization of bovine primordial follicles and their environment in vivo.

Classically, primordial follicles have flattened pre-granulosa cells that become cuboidal and divide during follicular activation. This change in shape is thus an index of activation. To examine this and follicular morphology in cattle, ovaries were processed for light and electron microscopy (n = 21). In single sections (5 microns thick), primordial follicles had a mean ratio of maximum to minimum diameters of 1.33 +/- 0.18 (mean +/- SD; n = 317, randomly selected), indicating that they had a prolate rather than a spherical shape. The prolate shape was attributable to clustering of granulosa cells at two opposite poles on the long axis of each follicle; and in each histological section, 82.5% of primordial follicles (n = 317) had at least one cuboidal granulosa cell. More accurate measurements of primordial follicles indicated that they had three dimensions measured as length (45.4 +/- 2.4 microns), breadth (26.8 +/- 1.5 microns), and depth (< 30.4 +/- 1.4 microns) (mean +/- SEM; n = 12, constructed from serial sections); a surface area of 0.0032 mm2; and 24 +/- 2 granulosa cells. The ultrastructural morphology of the cells of the bovine primordial follicle (n = 31 examined by electron microscopy) was similar to that of other species. The ovarian cortex was composed of discrete zones. The zones containing primordial follicles were substantially avascular, as observed by localizing von Willebrand factor, and rich in collagen fibrils. In conclusion, since primordial follicles of bovine ovaries contain some cuboidal pre-granulosa cells, changes in shape cannot be used with certainty as a marker of activation of bovine follicles.

Animals↗
PubMed1996

Effects of insulin-like growth factors and binding protein 1 on bovine granulosa cell division in anchorage-independent culture.

Granulosa cells can exhibit the properties of stem cells and tumour cells. Contact with neighbouring cells does not inhibit their replication in vivo and they can divide in vitro while embedded in agar and thus without anchorage on a substratum. By culturing granulosa cells without anchorage, those cells that do not require anchorage, and thus exhibit at least one property of stem cells, divide. The effects of insulin-like growth factors (IGFs) and insulin-like growth factor binding protein 1 (IGFBP-1) on the replication of such cells was investigated by isolating granulosa cells from follicles (3-5 mm diameter) from cyclic cows and culturing them in soft agar-methylcellulose solution. Cell division was measured as [3H]thymidine incorporation into DNA, total DNA, or as the amount of the nuclear La antigen. This antigen is involved in RNA synthesis and is expressed ubiquitously; here it was used to estimate the number of cells indirectly. Both IGF-I (100 ng ml-1) and IGF-II (100 ng ml-1) and their respective analogues, as well as insulin, all at the same concentration, significantly increased DNA synthesis as determined by [3H]thymidine incorporation (n = 5). An increase in the number of cells in the presence of IGF-I was also confirmed by DNA measurement (P < 0.05, n = 5) and by western immunoblotting analyses of La antigen (n = 3). IGFBP-1 significantly inhibited cell division stimulated by IGF-I (P < 0.001) and IGF-II (P < 0.001), but not that stimulated by the analogue, LR3IGF-I, which has low affinity for IGFBPs. Other factors also known to affect IGF synthesis or effectiveness (FSH, oestradiol, growth hormone) did not appear to influence division of granulosa cells when cultured under anchorage-independent conditions, while dibutyryl cAMP significantly inhibited cell division (P < 0.01, n = 5). In conclusion, IGFs have a role to play in stimulating division of stem-cell-like granulosa cells during follicular development and IGFBP-1 can specifically inhibit the mitogenic effects of IGFs.

Animals↗
PubMed1996

Different behavioural profiles of the R(+)- and S(-)-enantiomers of 8-hydroxy-2-(di-n-propylamino) tetralin in the murine elevated plus-maze.

(=) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been the most widely used pharmacological tool in research on 5-HT(1A) receptor function. In the present study, the behavioural effects of 8-OH-DPAT entantiomers were compared using an ethological version of the murine elevated plus-maze test. Subcutaneous pretreatment (-20min) with R(+)-8-OH-DPAT (0.03-1.0mg/kg) produced a pronounced; and dose-dependent behavioural suppression (decreased open/closed/total arm entries and increased nonexploratory behaviours). In contrast, over the same dose range, S(-)-8-OH-DPAT reduced several ethological indices of anxiety without altering the majority of conventional parameters or general activity levels, e.g. arm entries and per cent time measures, as well as head dipping. Findings are discussed in relation to differences in the intrinsic activity of 8-OH-DPAT isomers at 5-HT(1A) sites and the putative role of these receptors in anxiety-related processes. The differential behavioural profiles of 8-OH-DPAT enantiomers suggest that racemic 8-OH-DPAT may not be an ideal tool for research on the behavioural pharmacology of 5-HT(1A) receptors.

Journal Article↗
PubMed1995

Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.

Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis.

Animals↗
PubMed1995

Basal lamina and other extracellular matrix produced by bovine granulosa cells in anchorage-independent culture.

Bovine granulosa cells from 3-7 mm follicles were cultured without anchorage in soft agar/methylcellulose solution for 14 days, with or without 50 ng/ml basic fibroblast growth factor. The granulosa cells divided to form colonies of cells. These were analysed by light and electron microscopy, immunohistochemistry and Western immunoblotting. In approximately 20% of the colonies extracellular matrix was clearly visible at the light-microscope level. Ultrastructurally the matrix resembled a basal lamina 30-100 nm thick and was composed of tangled fibres or cords. Unidentified spherical structures of less than 50 nm diameter were sometimes present and attached to this basal lamina. The basal lamina of follicles had similar features, except that the basal lamina produced in vitro was a large aggregate of many convoluted layers. The cells produced collagen type IV and the cellular form of fibronectin. Intercellular areas not associated with basal lamina were identified. Ruthenium red staining revealed these areas to be rich in proteoglycan granules. Free granules were clustered near the cell surface, and the lumina of these areas were rich in fibres decorated with ruthenium red. This material did not resemble follicular fluid of antral follicles. Thus, granulosa cells in anchorage-independent cultures have a follicular cell morphology and secrete two distinct extracellular matrices, one similar to the follicular basal lamina.

Animals↗
PubMed1995

Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against alpha 2-adrenoceptor mediation.

The influence of alpha 2-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5-4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significant anxiolytic-like effects on standard spatiotemporal measures at 2.0-4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective alpha 2-adrenoceptor antagonist, idazoxan (0.63-5.0 mg/kg), exerted much weaker behavioural effects in the maze while the alpha 2-adrenoceptor agonist, clonidine (0.01-0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.

Animals↗
PubMed1995

Profile of action of 5-HT3 receptor antagonists, ondansetron and WAY 100289, in the elevated plus-maze test of anxiety of mice.

The effects of ondansetron (0.001-0.1 mg/kg) and the novel 5-HT3 receptor antagonist, WAY 100289 (0.01-10.0 mg/kg), on anxiety were examined in male mice using an ethological version of the elevated plus-maze paradigm. This procedure involves scoring specific aspects of defensive behaviour in addition to the more usual spatiotemporal measures. Results show that, at the doses tested, neither compound produced a behavioural profile consistent with anxiety reduction. Indeed, the lowest dose of ondansetron (0.001 mg/kg) produced some behavioural trends more typically associated with mild anxiety enhancement. Data are discussed in relation to the enigmatic effects of 5-HT3 receptor antagonists in animal models of anxiety. It is suggested that the large within- and between-test variability observed with these compounds may indicate an action on mechanisms other than anxiety.

Animals↗
PubMed1995

Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety.

Recent research employing the elevated plus-maze to assess anxiety in rodents has incorporated a variety of behavioral elements in addition to the standard parameters of entries onto and time spent in the aversive open arms. In the present study, we have used a large database comprising the behavioral profiles of 90 undrugged mice to examine the relationship between the standard spatiotemporal measures and a range of specific behaviors related to the defensive repertoire of the mouse. A factor analysis applied to the standard measures revealed two factors related to anxiety and locomotor activity. The simple addition of center time (an infrequently recorded measure) to the analysis yielded a third factor, most probably related to decision making. A large-scale factor analysis applied to all measures further confirmed the existence of factors related to anxiety, locomotor activity, and decision making, and revealed three further factors thought to represent risk assessment, vertical activity, and exploratory behavior. Thus, the inclusion of ethological measures not only confirmed prior knowledge based on a very limited range of measures, but also demonstrated the existence of additional behavioral dimensions. The potential applications of this knowledge are discussed.

Animals↗
PubMed1995

Ethological comparison of the effects of diazepam and acute/chronic imipramine on the behaviour of mice in the elevated plus-maze.

Recent clinical evidence suggests that the tricyclic antidepressant imipramine is effective against not only panic disorder but also generalized anxiety disorder. Although most animal models of anxiety appear to be insensitive to this agent, such work has almost invariably employed an acute treatment regimen. In the present study, ethological methods have been used to assess in detail the effects of acute and chronic imipramine treatment on the behaviour of male DBA/2 mice in the elevated plus-maze test. In contrast to acutely administered diazepam (1 mg/kg), which produced a significant anxiolytic profile on standard and ethological measures, neither acute nor chronic (daily, 15 days) treatment with imipramine (0-20 mg/kg) was associated with anxiety reduction. Data are discussed in relation to test sensitivity factors and the nonspecific mechanism of action of imipramine.

Animals↗
PubMed1995

Ethopharmacological analysis of the effects of putative 'anxiogenic' agents in the mouse elevated plus-maze.

The literature on the effects of anxiety-provoking agents in humans and animals is replete with inconsistent and contradictory findings as well as data that may have alternate explanations. To further our understanding in this area, ethological methods were used to assess in detail the effects of four putative anxiogenic agents in the murine elevated plus-maze test. Compounds studied were FG 7142 (1.25-10.0 mg/kg), pentylenetetrazol (PTZ; 1.875-30.0 mg/kg), isoproterenol (0.125-1.0 mg/kg), and sodium lactate (32.75-262.0 mg/kg). FG 7142 produced an anxiogenic-like profile at 10 mg/kg, an effect that could not be attributed to seizure activity or nonspecific behavioural suppression. PTZ exerted biphasic effects, with low doses (1.875-3.75 mg/kg) producing anxiolytic-like effects and high doses (20.0-30.0 mg/kg) anxiogenic-like effects. With the exception of the highest dose tested, which radically disrupted behavior, these effects of PTZ were also seen to be behaviorally specific. Although some minor behavioural changes were evident with sodium lactate and isoproterenol, neither compound altered anxiety-related measures under present test conditions. Data are discussed in relation to distinctions between anxiety and panic, and the nature of anxiety expressed in and detected by animal models.

Animals↗
PubMed1995

The antioxidant beta-carotene prevents covalent cross-linking between cholesterol side-chain cleavage cytochrome P450 and its electron donor, adrenodoxin, in bovine luteal cells.

Steroid hormones are an important class of hormones synthesized from cholesterol by a number of endocrine organs; including ovaries, placenta, testes and adrenal glands. The first and rate-limiting step in steroidogenesis is the cleavage of the side-chain of the cholesterol molecule, catalysed by a cytochrome P450 enzyme, cholesterol side-chain cleavage enzyme. This enzyme, as with other P450 enzymes, produces oxygen radicals. Oxygen free radicals can cause deleterious effects such as cross-linking and aggregation of proteins. Cells can protect against such damage with the use of antioxidants. The corpus luteum, or 'yellow body', of the ovary is very steroidogenic and is exceedingly rich in the yellow antioxidant, beta-carotene. The corpus luteum produces the steroid hormone progesterone that is needed to support pregnancy. Here we have shown that by depleting, or conversely repleting, luteal cells of their beta-carotene content in vitro that P450 side-chain cleavage enzyme became covalently non-disulfide cross-linked to its electron donor, adrenodoxin, and hence inactivated. Bovine luteal cells were cultured in 10% fetal calf serum with or without additional treatments for up to 72 h. Under control conditions the cellular levels of beta-carotene and alpha-tocopherol fell by 50% within 24 h and remained low. P450 side-chain cleavage enzyme become non-disulfide covalently cross-linked to its electron donor, adrenodoxin, as determined by Western immunoblotting (N = 18). Aminoglutethamide inhibited this cross-linking. The addition of beta-carotene at levels found in bovine serum, but not alpha-tocopherol or ascorbic acid, inhibited the degree of the cross-linking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenodoxin↗
PubMed1995

The physiology of the ovary: maturation of ovarian granulosa cells and a novel role for antioxidants in the corpus luteum.

During folliculogenesis the granulosa cells divide whilst in contact with each other, and so exhibit some of the characteristics of stem cells. In vitro we have shown that bovine granulosa cells from 3-7 mm follicles, like stem cells, divide without the need for a substratum, and produce colonies of cells. Growth factors, bFGF and IGF's, stimulate their division. These cells secrete and assemble a basal lamina, suggesting that the follicular basal lamina is produced by the granulosa cells. They have the morphological characteristics of follicular granulosa cells. Thus this system is ideal for studying the functions of immature granulosa cells because the cells do not spontaneously differentiate or luteinize into luteal cells, as occurs in culture on a substratum. On differentiation into luteal cells in vivo the cells express the steroidogenic enzymes for progesterone production and accumulate beta-carotene. During culture of bovine luteal cells we observed that a proportion of the steroidogenic enzyme cholesterol side-chain cleavage cytochrome P450 enzyme became chemically cross-linked to its electron donor, adrenodoxin. P450 enzymes produce oxygen free radicals and oxygen free radicals can cause cross-linking between proteins in close proximity. Cell protect against this damage by the use of antioxidant vitamins. Repleting the cultured luteal cells with beta-carotene reduced the amount of cross-linking. We conclude that the high levels of beta-carotene in corpora lutea are to protect against damage due to oxygen free radicals generated in the course of progesterone synthesis.

Adrenodoxin↗
PubMed1995

Concentrations of cytochrome P450 cholesterol side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase during prostaglandin F2 alpha-induced luteal regression in cattle.

Prostaglandin F2 alpha (PGF2 alpha)-induced regression of the corpus luteum causes both plasma progesterone concentrations and luteal concentrations of mRNA encoding the steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) to fall in parallel. To investigate the hypothesis that a decline in the concentrations of mRNA encoding steroidogenic enzymes causes plasma progesterone to fall, the luteal concentrations of the enzymes 3 beta-HSD and cytochrome P450 cholesterol side-chain cleavage were measured during induced luteolysis. Holstein heifers were treated with PGF2 alpha (25 mg Lutalyse) on Day 6 or Day 7 of the oestrous cycle and corpora lutea were collected 0 h, 2 h, 12 h, and 24 h later (n = 6, 4, 4, and 4 respectively). Analyses of the steroidogenic enzymes were carried out by Western immunoblotting. The luteal concentrations of both steroidogenic enzymes did not decrease over the 24-h period. It is concluded that, although the concentrations of mRNA encoding steroidogenic enzymes may decline in response to PGF2 alpha, this does not lead to a sufficiently rapid reduction in the concentrations of the enzymes to precede, and thus cause, the decline in plasma progesterone concentrations. Thus, the mechanism for the initial decline in plasma progesterone concentrations during luteolysis is still not known.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Cholecystokinin and anxiety: promises and pitfalls.

In the past 5 years, considerable interest has been expressed in the possible involvement of cholecystokinin (CCK) receptor mechanisms in anxiety disorders. Stemming from early clinical observations in the 1960s and electrophysiological findings some twenty years later, this interest now encompasses research on the behavioral effects of CCK receptor agonists and antagonists at both clinical and preclinical levels. The results to date have been encouraging enough to prompt a number of pharmaceutical companies to "fast track" the development of CCK receptor antagonists as antipanic agents. The present review critically assesses research findings in this area and concludes that the field is rife with inconsistency, the date are subject to a variety of methodological and interpretative pitfalls, and, unfortunately, the promise of therapeutic advance through CCK receptor antagonists may be illusory.

Animals↗
PubMed1994

Anxiolytic-like effect of (S)-WAY 100135, a 5-HT1A receptor antagonist, in the murine elevated plus-maze test.

The effects of (S)-WAY 100135 ((S)-N-tert-butyl-3-(4-(2-methoxyphenyl)- piperazin-1-yl)-2-phenyl-propanamide dihydrochloride; 2.5-20.0 mg/kg), a 5-HT1A receptor antagonist, on the behaviour of male mice were examined in the elevated plus-maze test of anxiety. An ethological scoring technique was used to provide a comprehensive profile of drug action. Only minor changes in behaviour were observed at 2.5 and 5.0 mg/kg, and consisted of reductions in some (though not all) risk assessment measures. At 10 mg/kg, the compound increased percent open arm entries and percent open arm time, without altering general activity levels. This classic anxiolytic-like profile was confirmed by major reductions in risk assessment measures including protected head-dips and protected stretched attend postures. Although many of the same changes were also observed at 20 mg/kg, the absence of an effect on percent open arm time and a tendency towards increased non-exploratory behaviour suggested (1) some loss of anxiolytic activity and (2) a possible contribution of non-specific factors at higher doses. Present findings indicate that (S)-WAY 100135 produces clear anxiolytic-like effects in the murine elevated plus-maze, a profile that can be distinguished from that produced by 5-HT1A receptor partial agonists in the same test.

Animals↗