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R J Rodgers

Publications and source records attributed to R J Rodgers.

At least 181 records · Page 10Linked to original sources

CGS 8216 fails to modify novelty-related behaviour in mice: further evidence for differential actions of benzodiazepine antagonists.

Recent evidence has indicated that, in rats, benzodiazepine antagonists exhibit low-dose intrinsic behavioural properties. In this study, the influence of CGS 8216 (1-20 mg/kg, i.p.) on the responsiveness of male mice to environmental novelty was examined. Unlike Ro 15-1788, which has previously been reported to enhance rearing under the present test conditions, analysis revealed that CGS 8216 was without effect on novelty-related responding. Results are discussed in relation to possible differences in the mode of action of various benzodiazepine antagonists.

Animals↗

Morphometry of the functional and regressing corpus luteum of the guinea pig.

A morphometric study of functional and regressing corpora lutea (CL) of guinea pigs (n = 5 per day) was performed on days 9, 12, and 16 of the estrous cycle. On day 9 the functional CL contained congruent to 750,000 cells, which included 565,200 +/- 56,700 (S.D.) endothelial cells or pericytes and 137,300 +/- 7,700 luteal cells. Between days 9 and 12 the only significant change suggesting the onset of regression was a reduction in vascular luminal surface area. During this time the number of luteal cells per CL increased to 204,400 +/- 34,800 (P less than .05), with an accompanying reduction in luteal cell volume from 19.8 +/- 1.8 to 14.4 +/- 2.4 pl/cell (P less than .01). The increase in cell numbers was explicable by cell division, with mitotic indices of 0.83% and 0.97% on days 9 and 12, respectively. Luteal volume was unaltered. Between days 12 and 16, the mean volume of a single CL fell from 3.98 +/- 0.2 to 1.42 +/- 0.3 mm3 (P less than .01) and luteal cell volume was reduced to 5.3 +/- 1.1 pl/cell (P less than .01). Between these 2 days the number of endothelial cells per CL fell from 539,900 +/- 75,500 to 144,400 +/- 63,300 (P less than .01), with an accompanying reduction in vascular luminal surface area and in the volume occupied by vascular lumina. The total number of luteal cells per CL was not reduced significantly. It was concluded that luteal cell numbers in the guinea pig increase up to the time of onset of luteal regression, and that during regression up to day 16, shrinkage of luteal cells is the major cause of loss of luteal volume. During regression, endothelial cell loss occurs much more rapidly than loss of luteal cells.

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Naloxone administration following brief exposure to novelty reduces activity and rearing in mice upon 24-h retest: a conditioned aversion?

It has recently been reported that naloxone treatment, prior to initial exposure to a novel arena, results in significant behavioural change when animals are retested 24 h later. In an attempt to clarify the nature of this delayed action of the opiate antagonist, three further studies have been performed. In the first experiment, male mice were injected with naloxone hydrochloride (0-10 mg/kg, IP) immediately after their initial experience of the test arena. When retested 24 h later, all groups that had previously received naloxone exhibited greatly reduced activity and rearing, with no evidence of a dose-response relationship. In the second experiment, naloxone (0-10 mg/kg) failed to induce a conditioned place aversion when administered according to the above regimen. In the final experiment, no evidence for a naloxone-induced taste aversion to saccharin was observed. It is concluded that the behavioural changes observed in the open-field study may reflect either (a) subtle aversive properties of naloxone which are insensitive to traditional one-trial paradigms or (b) opioid modulation of memory for non-painful experiences.

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Effects of the benzodiazepine antagonist Ro 15-1788 on social and agonistic behaviour in male albino mice.

In view of recently reported low-dose behavioural activity of Ro 15-1788, the present study examined the effects of this benzodiazepine antagonist on social and agonistic behaviours in adult male albino mice. Using a resident-intruder paradigm, independent pharmacological manipulation of interactants and pharmaco-ethological analysis, our data demonstrate significant behavioural effects of Ro 15-1788 in benzodiazepine-naive animals. In residents, treatment with the antagonist (1.25, 2.5, 10 and 20 mg/kg, IP) resulted in dose-related increases in offensive threat behaviour and reduced olfactory investigation. However, 5 mg/kg exerted no detectable behavioural action in these animals. In intruders, behavioural effects were observed only with 1.25 mg/kg Ro 15-1788, and consisted of a profile suggestive of reduced defensiveness. In both experiments, the behaviour of untreated opponents confirmed the existence of drug-induced behavioural changes in their partners. It is argued that present data are not inconsistent with the existence of putative endogenous benzodiazepine-like ligands and that the differential effects of Ro 15-1788 in residents (singly-housed) and intruders (grouped) suggest one possible explanation for previous failures to detect low-dose behavioural activity with this compound.

Aggression↗

Morphometric analysis and function in vivo and in vitro of corpora lutea from ewes treated with LHRH during seasonal anoestrus.

Ovulation was induced by 3 X 30 micrograms LHRH i.v. at 90-min intervals in anoestrous Corriedale ewes. Plasma LH surges occurred in all of 31 ewes given LHRH, but ovulation occurred in only 16 of these ewes. Luteal weight and plasma progesterone concentration were lower in ewes in which ovulation was induced during anoestrus than in cyclic control ewes in the breeding season, and when data from induced and control ewes were pooled luteal weight was strongly correlated with plasma progesterone concentration (r = +0.612, P less than 0.01). Five mature corpora lutea (CL) resulting from ovulation induced during anoestrus were compared by morphometric methods with 5 CL from cyclic control ewes. When data from induced and control CL were pooled, luteal volume was positively correlated with total number of cells per CL (r = +0.869, P less than 0.01) but negatively correlated with number of cells per mm3 luteal tissue (r = -0.676, P less than 0.05), i.e. smaller CL contained fewer cells, but more cells per unit volume. Relative numbers of large to small luteal cells, at approximately equal to 1:6, were similar in LHRH-induced and cyclic control CL. Large and small luteal cells were smaller in induced CL than in control CL, but cytoplasmic:nuclear ratio did not differ between induced and control CL. Basal and LH-stimulated progesterone production by dispersed luteal cells in vitro were lower for CL from LHRH-treated ewes than from controls. However, percentage increase in progesterone production in response to LH was not different between LHRH-treated and control ewes at any dose rate of LH used. It is concluded that the small size of CL induced by LHRH is due primarily to the low numbers and small volumes of the luteal cells in these CL, and that subnormal luteal weight and subnormal progesterone production per luteal cell contribute to the low plasma progesterone concentrations in ewes treated with LHRH during seasonal anoestrus.

Anestrus↗

Morphometric analysis of the cellular composition of the ovine corpus luteum.

An electron microscopical, morphometric study has been made of the cellular and non-cellular composition of the ovine corpus luteum fixed by perfusion, together with an estimate of total cell numbers in the corpus luteum based on measurement of cell and tissue DNA content. Normal cyclical corpora lutea from six ewes were studied by each method. Total cell numbers per corpus luteum were estimated at 258 X 10(6) by morphometry and 238 X 10(6) by DNA measurement. The existence of four structurally distinct major cell populations in ovine luteal tissue was confirmed. Percentages of the total cell number were as follows: large luteal cells - 4.2%; small luteal cells - 18.5%; fibrocytes - 16.8%; endothelial cells and pericytes - 52.6%. The remaining 7.9% comprised other miscellaneous cell types. Of the four major cell types, cell volume (X 10(3) micron 3 +/- standard error of the mean) was greatest for large luteal cells (13.08 +/- 2.10) and least for endothelial cells and pericytes (0.52 +/- 0.05), with small luteal cells (2.08 +/- 0.19) and fibrocytes (1.61 +/- 0.27) intermediate in size. Large luteal cells occupied 25.4% of luteal volume density, small luteal cells 17.5%, fibrocytes 11.2% and endothelial cells and pericytes 12.7%. Other cell types occupied 5.4%, with the remaining volume occupied by vascular lumina (10.8%) and intercellular space (17.1%). The data on cell volume support morphological findings suggesting that large and small luteal cells of the ovine corpus luteum are distinct populations rather than the upper and lower limits of a single population whose sizes are normally distributed. Of these two types of luteal cell, small luteal cells outnumbered large luteal cells by more than 4:1, while the individual large luteal cells were more than six times the mean volume of the small luteal cells. These facts need to be considered when assessing the relative contributions of the two types of luteal cell to overall luteal steroidogenic function.

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Social conflict activates status-dependent endogenous analgesic or hyperalgesic mechanisms in male mice: effects of naloxone on nociception and behaviour.

The concept of environmentally-induced activation of endogenous analgesia mechanisms rests, almost exclusively, upon studies which have involved the use of rather intense artificial stimuli. The current study was therefore designed to assess the validity of this concept under the more naturalistic conditions of social conflict between isolated resident mice and group-housed intruders. Agonistic experience was found to result in a potent, naloxone-reversible (10 mg/kg) analgesia in intruder mice while, in residents, it produced a moderate hyperalgesic reaction which was very sensitive to naloxone antagonism (0.1 mg/kg). Detailed videotape analyses revealed that only the behaviour of residents was significantly altered by naloxone treatment, with a highly selective inhibition of attack observed at 10 mg/kg. These data suggest that (1) social conflict in mice is a potent, and biologically-relevant, stimulus in the activation of endogenous naloxone-sensitive pain control mechanisms, (2) social status is an important determinant of nociceptive response to such experience and (3) inescapability from attack may be a critical factor in the development of encounter-induced analgesia.

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Naloxone partially antagonizes post-encounter analgesia and enhances defensive responding in male rats exposed to attack from lactating conspecifics.

Recent evidence indicates that inter-male conflict in mice, but not rats, results in opiate-like analgesia in defeated animals. To test the hypothesis that differences in attack intensity/controllability may underlie this apparent species difference, male rats were exposed to non-ritualized attack from lactating conspecifics. In response to such encounters, male intruders exhibited significant elevations in tail-flick latency. Pretreatment with low (0.1-1.0 mg/kg), but not high (10 mg/kg), doses of naloxone partially antagonized the development of post-encounter analgesia and enhanced several components of male defensiveness during encounters. These results suggest that exposure to attack from lactating conspecifics activates both opioid and nonopioid analgesia mechanisms in male intruders. Correlational analyses revealed, however, that intruder analgesia was not related to the number of attacks received or the display of submissive postures. Data are discussed with reference to the possible importance of psychological factors in the activation of endogenous pain inhibitory mechanisms in rats.

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Evidence for intrinsic behavioural activity of the benzodiazepine antagonist, Ro15-1788, in male mice.

It would be predicted that putative benzodiazepine should be released under anxiety-provoking conditions and that behavioural changes should be observed following pretreatment with selective antagonists of the benzodiazepine receptor. To test this hypothesis, adult male albino mice were briefly exposed to a novel, brightly-illuminated arena during the dark phase of their LD cycle. Under these test conditions, Ro15-1788 (10 mg/kg) enhanced total rearing whilst, a 5-10 mg/kg, it significantly altered the normal pattern of rearing over the test session. However, at the highest dose tested (20 mg/kg), such behavioural changes were no longer apparent. A similar, though non-significant, trend was observed for locomotor activity. These data, the first to demonstrate-low-dose intrinsic activity of Ro15-1788 in mice, suggest that benzodiazepine antagonists may prove to be powerful tools in the study of the behavioural significance of the benzodiazepine receptor.

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Large luteal cells the source of luteal oxytocin in the sheep.

To determine the cellular origin of oxytocin produced by the cyclical corpus luteum (CL) of the sheep, enriched fractions of enzymatically dispersed small and large luteal cells from 12 CL were prepared on a Ficoll 400 gradient. Oxytocin was measured by RIA. Large luteal cells contained 1.08 +/- (SD) 0.70 fg/cell oxytocin, which was congruent to 30 X the content of small luteal cells. Endothelial cells contained little if any oxytocin. During a 12-h incubation, large luteal cells produced 0.28 fg/cell.h oxytocin: small luteal cells did not produce measurable amounts of oxytocin. It is concluded that the large luteal cells are the source of the oxytocin produced by the CL of the sheep.

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Progesterone production in vitro by small and large ovine luteal cells.

Corpora lutea from cyclic ewes were dissociated by collagenase digestion and trypsin/EGTA treatment. Enriched fractions of endothelial cells, small luteal cells and large luteal cells were prepared on a stepped gradient of Ficoll 400. Progesterone was measured by radioimmunoassay and the results corrected so that progesterone production by each cell type could be determined. Endothelial cells did not produce significant amounts of progesterone, with or without LH stimulation, and endothelial cell contamination of small and large luteal cell fractions did not influence progesterone production by these fractions. Mean +/- s.e.m. basal progesterone production (n = 10) by large luteal cells was greater (P less than 0.001) on a per cell basis than that by small luteal cells (1.16 +/- 0.16 compared with 0.25 +/- 0.06 pg/h/cell). However LH, which stimulated a maximal 3-4-fold increase in progesterone production by small luteal cells (LH ED50 = 0.14 ng/ml), had no significant effect on production by large luteal cells, when contamination by small luteal cells was taken into account. The response of small luteal cells was specific to LH, other hormones having had no significant effect. Basal progesterone production by small luteal cells (0.12 +/- 0.03 fg/h/micron3) calculated per unit volume of cell was not significantly different from that of large luteal cells (0.17 +/- 0.02 fg/h/micron3). After LH stimulation, small luteal cells produced more progesterone than did large luteal cells (0.40 +/- 0.09 compared with 0.18 +/- 0.03 fg/h/micron3) (P less than 0.05). When the amounts of progesterone produced per cell were multiplied by the absolute numbers of large luteal (1 X 10(7] and small luteal (5 X 10(7] cells in the intact corpus luteum, basal progesterone production by large luteal cells (11.6 +/- 1.6 micrograms/h) was similar to that by small luteal cells (12.3 +/- 3.0 micrograms/h). However, under LH stimulation, progesterone production by the small luteal cell type (39.9 +/- 9.5 micrograms/h) was approximately 3 times greater than that by the large luteal cell type (12.3 +/- 1.6 micrograms/h) (P less than 0.05). We therefore conclude that small luteal cells may be the principal source of luteal progesterone production in the sheep.

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Delayed effects of naloxone on responsiveness to environmental novelty in rats.

Two experiments were conducted to examine further the hypothesized involvement of endorphins in responsiveness to environmental novelty. In Experiment 1, rats were treated with naloxone hydrochloride (0.5--5.0 mg/kg, SC) before initial exposure to a novel arena (Day 1) and then retested in the area 24 h later (Day 2). Only naloxone (5 mg/kg) significantly affected Day 1 performance, producing a selective reduction in locomotor activity. However, compared to saline controls, all groups that had previously received naloxone showed marked reductions in both locomotor activity and rearing upon Day 2 retest. In Experiment 2, naloxone (0.5--5.0 mg/kg) was without significant effect on performance in naive animals which had been injected on Day 1 but not exposed to the arena until Day 2. These data suggest that the delayed effects of naloxone relate specifically to the initial experience of environmental novelty rather than receptor changes or metabolite influences resulting from acute antagonist treatment. Results are discussed in relation to a possible action of naloxone upon mechanisms of attention and/or memory.

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Differential effects of naloxone and diprenorphine on defensive behaviour in rats.

Two opiate antagonists, naloxone and diprenorphine, were used to examine the proposed involvement of endogenous opioid mechanisms in the modulation of shock-induced defensive behaviour patterns in rats. Naloxone was found to exert a biphasic influence on defensive fighting, with small dose (0.1 mg/kg) facilitation and large dose (10 mg/kg) inhibition. This compound also induced a dose-dependent inhibitory effect on shock-elicited threat whilst facilitated escape/avoidance behaviour was observed with the largest doses only. None of these influences could be attributed to alterations in electric shock thresholds. In contrast to the effects of naloxone, diprenorphine (0.1-10 mg/kg) was largely ineffective in modifying shock-induced defensive behaviour. These data suggest that endogenous opioid mechanisms may not be involved in the effects of naloxone on defensive fighting and cast some doubt upon the general hypothesis of the involvement of endorphins in the regulation of innate defence patterns.

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Agonistic behaviour in rats: evidence for non-involvement of opioid mechanisms.

It has recently been proposed that a stress-activated, endogenous analgesia mechanism would be adaptive in situations in which pain perception might otherwise disrupt effective behavioural performance. In a semi-natural test situation, the current study examined two predictions arising from this hypothesis: (1) in a manner analogous to other stressors, agonistic experience should produce analgesia and, if naloxone-sensitive opioid mechanisms are implicated, then (2) pretreatment with naloxone should block the development of this response and alter the displayed behaviour patterns. Neither prediction was substantiated by the data. Experience of an agonistic encounter failed to produce analgesia in either resident or intruder animals. Furthermore, naloxone hydrochloride (1-25 mg/kg) was also without effect on patterns of offense or defense. Data are discussed in relation to the critical nature of the stimulus factors involved in the activation of endogenous analgesic mechanisms and the postulated involvement of such mechanisms in biologically-adaptive behaviours.

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Effects of a synthetic prostaglandin analogue, cloprostenol, on the corpus luteum of the guinea pig.

The effects of a synthetic prostaglandin analogue, cloprostenol, on luteal function in the guinea pig were studied. At a dose of 250 micrograms, cloprostenol administered I-P on day 9 of the cestrous cycle caused a reduction in the length of the oestrous cycle from 17.4 +/- s.d.0.9 to 14.5 +/- 1.1 days (p less than 0.01). Lower doses were ineffective, and post-treatment cycles were not different in length from pre-treatment cycles. Cloprostenol also caused a dose-dependent reduction in luteal weight, which fell from 3.52 +/- 0.82 to 1.82 +/- 0.41mg (p less than 0.01) 48 h after administration of a 250 micrograms dose on day 9. Plasma progesterone, measured by radioimmunoassay, was reduced from 4.67 +/- 0.59 to 2.69 +/- 0.66 ng ml-1 (p less than 0.01) 48 h after administration of 250 micrograms cloprostenol on day 9. 250 micrograms cloprostenol also reduced blood flow per corpus luteum, measured by 85Sr-labelled 15 microns microspheres, both at 3 h (20.20 +/- 10.36 to 9.40 +/- 4.20 microliters min-1; p less than 0.05) and at 48 h (18.47 +/- 8.27 to 5.23 +/- 1.90 microliters min-1; p less than 0.01) after administration on day 9. No adverse side-effects were observed at any dose level of cloprostenol used. It was concluded that cloprostenol is a useful experimental luteolysin in the guinea pig.

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GABAergic influences on defensive fighting in rats.

The involvement of GABAergic mechanisms in shock-induced defensive fighting in rats was investigated in a series of three experiments. In Experiment 1, sodium n-dipropylacetate (100-200 mg/kg) failed to produce significant behavioural change whilst gamma-vinyl-GABA (100-200 mg/kg) induced a selective and dose-dependent reduction in fighting. In Experiment 2, although inconsistent behavioural effects were obtained with (+)-bicuculline (0.25-4 mg/kg), a biphasic influence on defensive fighting was observed with picrotoxin (0.125-2 mg/kg). The inhibitory effect on fighting, induced by the highest dose of picrotoxin, was related to motor impairment. In Experiment 3, muscimol reduced fighting at doses above 0.25 mg/kg with motor disruption evident only at the highest dose used (1 mg/kg). A dose-dependent inhibition of defensive fighting was observed with 1-baclofen (0.15-1.2 mg/kg) which, at the highest dose tested, also impaired motor coordination. None of the compounds tested significantly altered shock thresholds. Results are discussed in relation to the hypothesized inhibitory role of GABA in the mediation of aggressive behaviours.

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Purification, morphology, and progesterone production and content of three cell types isolated from the corpus luteum of the sheep.

A method is presented for the isolation and purification of three cell types, endothelial cells, small luteal cells and large luteal cells, from the ovine corpus luteum. The method involves enzymatic dispersion of luteal tissue followed by centrifugation of separated cells on a Ficoll gradient. The three purified cell types and others, particularly fibrocytes and smooth muscle cells, that were removed during purification, were identified by their morphology. The cell yield, the cellular composition and cellular progesterone content of each fraction from the Ficoll gradient were measured. The endothelial cell fractions were relatively free of contamination by other cell types and had negligible progesterone. Fractions of small luteal cells and those of large luteal cells contained endothelial cells but were relatively free of other cell types. Large luteal cells contained significantly more progesterone, produced more progesterone when incubated in culture, but were less responsive to luteinizing hormone than small luteal cells.

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