Biomedical subjects

R J Rodgers

Publications and source records attributed to R J Rodgers.

12 recordsLinked to original sources

PubMed1992

Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699.

Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model.

Analgesia↗

PubMed1992

The role of bovine lipoproteins in the regulation of steroidogenesis and HMG-CoA reductase in bovine adrenocortical cells.

The sources of cholesterol for steroid hormone production were examined using bovine adrenocortical (BAC) cells in primary culture. The experiments were designed to determine the effects of lipoproteins on cortisol production and the level of BAC cell 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Most studies on BAC cell lipoprotein requirements have been conducted using human low-density lipoprotein (hHDL); none have used the homologous bovine lipoproteins. BAC cells treated with corticotropin (ACTH) in a medium devoid of lipoproteins increased and maintained cortisol production 7- to 20-fold above basal levels. Under such conditions ACTH also increased the rate of HMG-CoA reductase activity. Inhibition of HMG-CoA reductase with mevinolin inhibited cortisol production by 85%, indicating that the cells were using cholesterol synthesized de novo for steroid production. Cortisol production was increased almost 40-fold above basal levels if hLDL (100 micrograms/ml) was included in the incubation medium. Human LDL also suppressed the levels of HMG-CoA reductase in a concentration-dependent fashion. Human HDL was without effect on either BAC cell steroidogenesis of HMG-CoA reductase. Addition of bovine LDL (bLDL) to the incubation medium also caused an increase in cortisol production and inhibited cholesterol synthesis. By contrast to hHDL, bHDL (100 micrograms/ml) increased the ability of BAC cells to produce cortisol production. Bovine HDL (bHDL) also was able to decrease HMG-CoA reductase, but not to the extent caused by hLDL or bLDL. These data demonstrate that bovine adrenal cells can use bHDL as a source of cholesterol for steroid hormone production. These findings may be of particular importance when one considers that in vivo, the bHDL content of bovine serum greatly surpasses the level of bLDL.

Adrenal Cortex↗

PubMed1979

Effects of nicotine, mecamylamine, and hexamethonium on shock-induced fighting, pain reactivity, and locomotor behaviour in rats.

Three series of experiments were performed to evaluate possible nicotinic cholinergic influences on fighting behaviour in rats. Each series consisted of three tests (naive animals in each test); shock-induced fighting, pain threshold estimation and locomotor activity. In the first series, nicotine (0.25 -- 1.00 mg/kg) was found to produce a dose-dependent inhibition of fighting without altering shock thresholds. However, the highest dose used also significantly reduced rearing in the activity test. In the second series, mecamylamine (a centrally active antinicotinic) produced a facilitation of fighting at low doses (2.5 mg/kg) and an inhibition at higher doses (10 mg/kg). Whilst these effects were unrelated to changes in shock thresholds, the high dose resulted in a reduction in both horizontal activity and rearing. Finally, as a control for possible peripheral effects of nicotinic blockage, a third series examined the behavioural effects of hexamethonium. Low doses of this compound (2.25 -- 4.5 mg/kg) had little effect on fighting whilst higher doses (9 -- 18 mg/kg) attenuated these responses. Interestingly, although hexamethonium had no effect on shock thresholds, the highest dose (18 mg/kg) produced a facilitation of horizontal activity. Results are discussed in relation to the hypothesis of central nicotinic cholinergic inhibition of agonistic behaviour.

Aggression↗

PubMed1979

Effect of naloxone on the behaviour of rats exposed to a novel environment.

It has recently been suggested that endogenous opiates may play a general role in stress responding. To test this hypothesis, naloxone hydrochloride (0.5-4.0 mg/kg SC) was administered to rats exposed to an open field situation. Naloxone treatment produced a decrease in locomotor activity and rearing, and an increase in defaecation. A simple dose-response relationship was not observed, with the most potent effects exerted by the 1 mg/kg dose. Nvertheless, these results indicate that naloxone increases emotionality in the rat and suggest that opioid peptides may be released under conditions of nonpainful stress.

Animals↗

PubMed1979

Exploratory behaviour and aversive thresholds following intra-amygdaloid application of opiates in rats.

Rats were bilaterally implanted with guide cannulae aimed at the central or medial nucleus of the amygdala. Microinjections of morphine (10 microgram) at both sites significantly elevated the threshold of response in the flinch-jump test; but only at medial sites did naloxone (1 microgram) antagonise this effect. However, in the hole-board test, an opposite pattern of results emerged. Morphine injections into the central nucleus produced naloxone-reversible reductions in both exploration and activity whilst, in the medial nucleus, the morphine-induced decrease in exploration was not reversed by naloxone. It is concluded that (1) the presence or absence of naloxone-sensitive opiate receptors cannot always be deduced on the basis of a single behavioural test and (2) within the amygdaloid complex, two distinct naloxone-sensitive opiate systems appear to be involved in the modulation of behavioural responses to different forms of stimulation.

Amygdala↗

PubMed1979

Partial anxiolytic action of morphine sulphate following microinjection into the central nucleus of the amygdala in rats.

In the social interaction test of anxiety, bilateral microinjections of morphine sulphate (10 microgram) into the central nucleus of the amygdala counteracted the reduction in social interaction normally seen when the test arena is unfamiliar to rats. However, these injections did not counteract the decrease in social interaction that is observed as illuminance of the arena is increased. Morphine injections into the medial site depressed social interaction below the levels shown by control animals. In the open field test, morphine produced a facilitation of peripheral activity when injected into the central nucleus whilst a decrease in rearing was observed following similar injections into the medial nucleus. Overall, these data indicate a partial anxiolytic action of morphine in the central amygdaloid nucleus. Results are discussed in relation to possible differences in opioid peptide innervation of these two amygdaloid nuclei.

Amygdala↗

PubMed1979