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Biomedical subjects

R J Rodgers

Publications and source records attributed to R J Rodgers.

At least 127 records · Page 7Linked to original sources
PubMed1992

Morphine attenuates antipredator ultrasonic vocalizations in mixed-sex rat colonies.

Mixed-sex groups of laboratory rats living in a visible burrow system (VBS) emit 18-27 kHz ultrasound and retreat to the burrow when a cat is placed in the open area of the VBS. The total duration of ultrasonic vocalizations was reliably reduced by pretreatment with 5 mg/kg morphine. In a subsequent study using male-female colony pairs, presentation of a cat to individual rats in the absence of their colony mate indicated significant gender differences in base frequency, degree of emission, and characteristics of pulses elicited. Specifically, females showed a greater number and duration of vocalizations, of higher frequency (kHz), and with shorter individual pulse durations than males. In the same study, morphine (5 mg/kg) produced a general decrease in the level of ultrasonic emissions in both sexes, reduced the mean base frequency (kHz), and increased the mean duration of individual pulses. These data suggest that endogenous opioid mechanisms may be involved in the mediation of ultrasonic vocalization in response to a predator, and are discussed with reference to known involvement of such systems in defensive responding.

Animals↗
PubMed1991

Effects of benzodiazepine receptor antagonist, flumazenil, on antinociceptive and behavioural responses to the elevated plus-maze in mice.

Brief exposure to an elevated plus-maze has been shown to induce antinociception in male mice, a reaction that is not attenuated by manipulations of opiate receptors but which is fully blocked by diazepam. The present study examined the effects of the benzodiazepine receptor antagonist, flumazenil (5-20 mg/kg), on behavioural and antinociceptive responses to the elevated plus-maze in male DBA/2 mice. The results showed that, in the absence of an effect on total arm entries or rearing, flumazenil increased the time spent on the closed arms of the maze (an anxiogenic profile) and significantly enhanced antinociception induced by the elevated plus-maze. Data are discussed in relation to an "endogenous ligand theory" and it is concluded that the present findings are consistent with the proposed involvement of anxiety in at least certain forms of adaptive inhibition of pain.

Analgesia↗
PubMed1991

"Paradoxical" effects of morphine on antipredator defense reactions in wild and laboratory rats.

In a Fear/Defense Test Battery, measuring defensive reactions to a present, approaching and contacting predator, the highest dose of morphine tested (7.5 mg/kg) reliably reduced vocalization to dorsal contact, to vibrissae stimulation, and to an anesthetized conspecific in laboratory-bred wild R. norvegicus. Except for a dose-dependent reduction in flinch/jump reactions to dorsal contact (taps), other defensive behaviors (flight, freezing, etc.) were not reliably altered by morphine treatment (0, 1.0, 2.5, 7.5 mg/kg). Vocalization responses to vibrissae stimulation in wild-trapped R. rattus were reliably increased following naloxone (1.0 and 10.0 mg/kg) administration, lending support for opiate receptor involvement in the mediation of defensive vocalization. In the Anxiety/Defense Test Battery, measuring defensive reactions to situations associated with a predator (cat) or with cat odor, laboratory rats showed no decrease in defensive behavior with morphine (0, 1.0, 5.0 mg/kg). In direct contrast to the above findings, the effects of morphine treatment in this test battery suggested a generalized increase in defensiveness to noncontacting and nonpainful threat stimuli. These effects included a decrease in time spent near the cat compartment, with a complementary increase in time spent at maximum distance, a decrease in transits between these sections, an increase in crouching, and a decrease in grooming and rearing. This pattern of results suggests that morphine may have two opposing effects on defensive behavior, a generalized enhancement, together with a more specific reduction of responses to tactile or painful stimulation. A very widespread pattern of reliable sex or sex x drug effects in the Anxiety/Defense Test Battery was in good agreement with previous reports of sex differences in these tests, with females generally more defensive than males. Consonant with previous findings, no reliable sex differences were found with the Fear/Defense Test Battery, although several values approached an acceptable level of statistical significance.

Animals↗
PubMed1991

Differential effects of novel ligands for 5-HT receptor subtypes on nonopioid defensive analgesia in male mice.

The effects of a number of 5-HT receptor ligands were examined on nonopioid defensive analgesia in male DBA/2 mice. MDL 73005EF (0.05-1.0 mg/kg), a selective 5-HT1A receptor agonist, potently and dose-dependently inhibited the analgesic consequences of social defeat. CGS 12066B (0.5-10.0 mg/kg) and MK-212 (0.3-10.0 mg/kg), selective agonists for 5-HT1B and 5-HT1C sites, respectively, failed to influence this particular form of adaptive pain inhibition. Two 5-HT2/1C receptor antagonists, ritanserin (0.05-10.0 mg/kg) and ICI 169.369 (0.3-10.0 mg/kg), were also devoid of specific effects upon defensive analgesia. Both ritanserin and ICI 169,369 were found to have intrinsic analgetic efficacy and to induce behavioural changes indicative of increased defensiveness. These data, together with previous findings, confirm the specific involvement of 5-HT1A receptor mechanisms in the analgesic consequences of social defeat in male mice. Results are discussed in relation to the role of anxiety in adaptive pain inhibition.

Aggression↗
PubMed1991

Cloning of the inhibin/activin beta B subunit gene from the Booroola merino sheep.

The gene encoding the inhibin/activin beta B subunit was isolated from a Booroola Merino ewe which had two copies of the unidentified fertility gene. Both the DNA sequence (greater than 87%) and amino acid sequence (greater than 93%) were highly homologous to those of the human and rat genes. The upstream region of the gene was similar to that of the human and rat genes, having SP1 binding sites and no TATA or CAAT boxes and, like that of the rat, but unlike that of the human gene, no cyclic AMP response elements, suggesting that the beta B gene of sheep and rats is regulated differently from that of man.

Activins↗
PubMed1990

Stereospecific inhibition of non-opioid defeat analgesia in male mice by MDL 72832, a selective 5-HT1A receptor agonist.

The effects of MDL 72832, a potent and stereoselective ligand for 5-HT1A sites, on basal nociception and non-opioid defeat analgesia in male mice were examined. Neither (+)- nor (-)-MDL 72832 significantly altered basal tail-flick latencies. In contrast, (-)-MDL 72832 potently inhibited defeat analgesia (0.1-0.5 mg/kg i.p.), with similar effects produced by (+)-MDL 72832 only at substantially higher doses (3.0-5.0 mg/kg i.p.). These data clearly demonstrate a stereoselective action of this 5-HT1A ligand on non-opioid defeat analgesia.

Analgesia↗
PubMed1990

8-OH-DPAT specifically enhances feeding behaviour in mice: evidence from behavioural competition.

The behavioural specificity of the hyperphagic effects of 8-OH-DPAT is a controversial issue. The present study addressed this question through the introduction of behavioural competition. Feeding behaviour in male mice was assessed under both basal (free-feeding) and social conflict conditions. Since, in the latter condition, defence and escape are prepotent responses, elicitation of feeding would be indicative of a specific treatment effect on mechanisms controlling food intake. Results showed that 8-OH-DPAT enhanced basal feeding duration (at doses of 0.05-0.50 mg/kg) and also elicited feeding in intruder mice during encounters with aggressive resident conspecifics (at doses of 0.10-0.50 mg/kg). As the 5-HT3 antagonist GR38032F (1.0-2.0 mg/kg) enhanced feeding only under basal conditions, the effect of 8-OH-DPAT cannot readily be attributed to anxiety reduction. Finally, diazepam (1.0-2.0 mg/kg) produced a similar profile to that of 8-OH-DPAT, suggesting that the hyperphagic effects of the 5-HT1A agonist are not pharmacologically specific.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Diazepam changes risk assessment in an anxiety/defense test battery.

An anxiety/defense test battery was designed to assess defensive reactions of laboratory rats to situations associated with nonpainful threat (exposure to a cat). The battery measured three defense patterns, movement inhibition, risk assessment behaviors, and inhibition of nondefensive behaviors, in two tasks. Diazepam (4.0 mg/kg) altered four of five risk assessment measures, but failed to show an anxiolytic effect on movement inhibition, and had minimal and inconsistent effects on inhibition of nondefensive behaviors. The risk assessment changes with diazepam were all consistent with an anxiolytic action of diazepam. These results provide a partial contrast to the general lack of anxiolytic action of diazepam in a fear/defense test battery designed to measure reactions to a discrete, present, threat stimulus, and suggest a greater diazepam effect on risk assessment than on other aspects of defensive responding. Sex differences indicating higher defensiveness for female than male rats were obtained on many of these measures.

Animals↗
PubMed1990

Antinociceptive effects of elevated plus-maze exposure: influence of opiate receptor manipulations.

It has been suggested that anxiety may be a critical factor in certain forms of non-opioid environmental analgesia. In the present study, 5-min exposure to the elevated plus-maze test of anxiety (EPM) induced a mild, though enduring, elevation in tail-flick latencies in male mice. Pretreatment with the opiate antagonist naltrexone (0.1-10.0 mg/kg) failed to block EPM-induced antinociception: indeed, the highest dose actually enhanced the response. This effect could not be attributed to intrinsic analgetic activity of naltrexone. Rather, analysis of EPM behaviours suggested that it may have been secondary to an anxiogenic effect of the compound. The involvement of non-opioid substrates in the form of pain inhibition was further supported by the failure of chronic morphine treatment (7 days; 7.5 mg/kg) to alter either the antinociceptive or behavioural response to EPM exposure. Irrespective of treatment history, mice showed a retest EPM profile of enhanced anxiety, with tail-flick data suggesting a major contribution of anticipatory factors. Several important methodological variables are discussed and findings are contrasted with parallel studies on non-opioid defeat analgesia.

Animals↗
PubMed1990

Highly potent inhibitory effects of 5-HT3 receptor antagonist, GR38032F, on non-opioid defeat analgesia in male mice.

Behavioural and pharmacological evidence indicates that non-opioid analgesia in defeated male mice is initiated by anxiety and that serotongergic (5-HT) substrates are implicated. In the present study, the effects of the novel putative 5-HT3 anxiolytic, GR38032F, on this form of adaptive inhibition of pain have been examined. The results showed that defeat analgesia was totally inhibited by 1 microgram/kg-1 mg/kg of GR38032F, with partial inhibition evident over the dose range of 0.0001-0.1 microgram/kg and loss of efficacy at smaller doses. These highly potent effects of GR38032F are consistent with its anxiolytic profile in animal models and cannot be accounted for by indirect actions on basal nociception. These findings point to a potentially important modulatory role for 5-HT3 receptor mechanisms in defeat analgesia and, more generally, provide further evidence for the involvement of 5-HT in the mediation of non-opioid forms of environmentally-induced antinociception.

Analgesia↗
PubMed1990

Effects of scopolamine on antipredator defense reactions in wild and laboratory rats.

Two experiments were designed to investigate the effects of scopolamine hydrobromide (0.25-1.0 mg/kg), and its methyl derivative, on the defensive reactions of rats to nonpainful threat stimuli. In the first experiment, over the dose range studied neither compound significantly altered avoidance, freezing, defensive threat or attack in wild Rattus rattus confronted by the experimenter and other predator-related stimuli. Scopolamine hydrobromide did, however, produce a dose-dependent increase in flight distance; this effect was not seen with the methyl compound, confirming central cholinergic mediation. In the second experiment, no dose of either compound significantly altered the behaviour of Long-Evans rats prior to cat exposure. During cat exposure, however, scopolamine hydrobromide (but not methyl scopolamine) increased the amount of time spent in the vicinity of the cat, increased scanning and rearing, and reduced grooming behaviour. Although reliable, the latter effects were not pronounced. Together, these data do not support a major involvement of central muscarinic receptor mechanisms in the regulation of defensive patterns in wild or laboratory rats.

Aggression↗
PubMed1990

Secretion and gene expression of inhibin, oxytocin and steroid hormones during the in vitro differentiation of bovine granulosa cells.

Bovine granulosa cells were cultured under defined conditions to examine (1) their secretion of immunoreactive inhibin, oxytocin, progesterone and oestradiol during differentiation in vitro; (2) their expression, by Northern analysis, of specific mRNAs for inhibin and oxytocin as compared with uncultured cells; (3) possible interrelationships between the four secreted hormones; and (4) the hypothesis that androgens and steroidogenesis influence the secretion of inhibin. The secretion of inhibin and oestradiol fell rapidly over the first few days of culture but remained at detectable levels for at least 7 days. Conversely, the secretion of oxytocin and progesterone rose steadily as culture progressed. These changes occurred spontaneously (i.e. without gonadotrophin treatment) and were not dependent on the addition of serum to the culture medium. Messenger RNAs for the inhibin alpha- and beta A-subunits were present in uncultured cells but barely detectable or undetectable in cells cultured for 4 days. Conversely, the mRNA for oxytocin, which was not detectable in uncultured cells, was present in cultured cells and increased in quantity as culture progressed. Treatment of cells with testosterone (5 nM-5 microM), in the presence or absence of serum (10% FCS), had no effect on the secretion of inhibin but stimulated the declining oestradiol secretion. Treatment with ascorbic acid (0.5 mM) increased the secretion of oxytocin and progesterone, as previously described, but not that of inhibin. Treatment with aminoglutethimide (0.5 mM), an inhibitor of steroidogenesis, substantially inhibited progesterone secretion and the response of oestradiol secretion to testosterone, but had no effect on the secretion of either inhibin or oxytocin. We conclude that bovine granulosa cells differentiate spontaneously in defined culture in a manner that, as defined by the secretion of steroid and peptide hormones, closely resembles their luteinization in vivo. The switch in protein hormone secretion from inhibin to oxytocin is accompanied by a corresponding change in mRNA expression. The changes in steroid and peptide hormone secretions that take place in culture appear to occur independently of one another although their absolute cause remains to be determined. In contrast to previous studies, we could find no evidence for the regulation of inhibin secretion by either androgens or steroidogenesis.

Animals↗
PubMed1990

Ultrastructural cytology of the cyclic corpus luteum of the cow.

Corpora lutea (CL) from cows on day 12 of the oestrous cycle were studied by electron microscopy to investigate whether, and how, different subpopulations of luteal cells can be identified in tissue sections. Tissues from 6 CL were examined, and nucleated profiles of luteal cells were classified as large, medium or small on the basis of their areas in electron micrographs. Cut-off points for area categories for large, medium and small-sized cells were based on diameters of greater than 25, 20-25 and less than 20 microns, respectively, if the measured areas were converted to a circular shape after correction for shrinkage. The only qualitative features which distinguished cells of large size from those of small size were the presence of clusters of secretory granules, and of exocytosis of these granules, in large cells only. However, these features were observed in only 59% of large cells, probably primarily due to sampling limitations in single sections. Other qualitative features which have been regarded as diagnostic of large or small luteal cells were observed in cells in all size categories. It was concluded that large and small luteal cells in the cyclic CL of the cow are distinguishable by their ultrastructural features. However, these data do not support the recent suggestion that the mid-cycle CL of the cow contain two subpopulations of large luteal cells in approximately equal numbers.

Animals↗
PubMed1989

Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines.

A battery of tests designed to elicit reactions to a variety of non-painful threat stimuli was used to study the effects of chlordiazepoxide (5-20 mg/kg), diazepam (1-5 mg/kg) and midazolam (1-10 mg/kg) on the defensive repertoire of wild Rattus rattus. The most consistent effect of benzodiazepine treatment, across compounds and tests, was a marked reduction in defensive threat and attack behaviors, with midazolam effective over a wider range of situations. In contrast, effects on freezing and flight reactions were more variable, differing substantially as a function of stimulus context. The general profile of observed changes in defense cannot be explained in terms of either non-specific behavioral suppression or a global reduction in defensiveness. Rather, our findings suggest that benzodiazepines may primarily induce a shift within the defense repertoire.

Aggression↗
PubMed1989

5HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), inhibits non-opioid analgesia in defeated mice: influence of route of administration.

Recent studies have suggested that anxiety may be an important factor in the non-opioid analgesic response to defeat in muroid rodents. In the present study, we have examined the influence of the 5-HT1A receptor agonist, 8-OH-DPAT, on basal nociception and defeat analgesia in male DBA/2 mice. Our results show that, while devoid of intrinsic activity on the mouse tail-flick assay, 8-OH-DPAT blocks the analgetic consequences of defeat. A ten-fold potency differential was observed as a function of route of injection, with minimum effective doses of 0.1 and 1.0 mg/kg for subcutaneous and intraperitoneal administration, respectively. Although further studies are required, these preliminary data support 5-HT1A receptor involvement in the mediation of this form of adaptive pain inhibition.

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