Biomedical subjects

H C Jackson

Publications and source records attributed to H C Jackson.

At least 55 records · Page 3Linked to original sources

PubMed1991

Investigation of the different types of opioid receptor involved in electroconvulsive shock-induced antinociception and catalepsy in the rat.

The effects of novel opioid antagonists on the behavioural syndrome induced by electroconvulsive shock (ECS) in rats have been examined and compared with those of the established agent naloxone. A single ECS produced catalepsy and significantly increased tail immersion response times during the 15 min following the seizure. These responses were inhibited by a low dose of naloxone (1 mg kg-1, i.p.) and also by RX8008M (16-methylcyprenorphine; 1 mg kg-1, i.p.) which blocks mu- and delta- but not kappa-opioid receptor function. In comparison, the antinociception and catalepsy induced by ECS was not attenuated by the selective delta-receptor antagonist naltrindole (1 mg kg-1, i.p.). These results suggest that ECS-induced antinociception and catalepsy may be mediated by endogenous opioids acting at mu-opioid receptors and are consistent with biochemical studies showing the release of beta-endorphin in both animals and man following this procedure.

Analgesia↗

PubMed1990

Body temperature discriminates between full and partial benzodiazepine receptor agonists.

The benzodiazepine full agonist loprazolam and the beta-carboline ZK 93423 produced hypothermia in mice (1-30 mg/kg i.p.). Maximal effects were seen at relatively low doses of these compounds. In contrast, the partial agonists Ro 17-1812 (a benzodiazepine) and ZK 91296 (a beta-carboline), did not modify rectal temperature at doses up to 30 mg/kg i.p. (which would be receptor saturating). Body temperature may therefore be a useful test for discriminating between full and partial agonists at the benzodiazepine receptor.

Animals↗

PubMed1990

Noradrenergic mechanisms appear not to be involved in cocaine-induced seizures and lethality.

In the present study we have investigated the effects of compounds which increase synaptic levels of noradrenaline on cocaine-induced seizures and lethality in mice. The noradrenaline uptake blocker desipramine (0.3, 3, 30 mg/kg i.p.; 1h pretreatment) and the alpha 2-antagonists idazoxan (0.05, 0.5, 5 mg/kg i.p.; 15 min) and RX811059A (0.01, 0.1, 1 mg/kg i.p.; 15 min) neither reduced nor increased the number of animals having convulsions in the 10 min following administration of cocaine (45, 60 mg/kg i.p.). None of these drugs increased lethality when assessed 10 minutes after 60 mg/kg cocaine and the alpha 2-antagonists did not protect against the lethal effects of a 90 mg/kg dose. On the other hand, desipramine significantly reduced the number of animals dying after this high dose of cocaine. These results suggest that noradrenergic mechanisms do not promote cocaine-induced convulsions and lethality - an important observation in light of the growing use of desipramine for initiation of abstinence in cocaine-dependent outpatients.

Adrenergic alpha-Antagonists↗

PubMed1990

Lack of effect of perinatal lead exposure on kappa-opioid receptor function.

The effects of lead exposure have been studied upon the behavioural and diuretic responses to the kappa-opioid receptor agonist U-50488H in neonatal rats. Lead was administered in the maternal drinking water (100, 300 and 1000 ppm) from conception to postnatal day 14. The hyperactivity, wall climbing behaviours and diuretic effects of U-50488H (0.1-30 mg/kg, i.p.) in 5- and 20-day-old rat pups were unaffected at all 3 lead dose levels. Lead treatment per se produced a decrease in activity at 20 days. These results contrast with our previously reported disruption of mu- and delta-opioid receptor systems following perinatal lead exposure and suggest that the toxic effects of this metal may be confined to particular types of opioid receptor.

Animals↗

PubMed1989

Behavioural effects of selective mu-, kappa-, and delta-opioid agonists in neonatal rats.

The behavioural effects of selective mu-, kappa- and delta-opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to mu-agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (D-Ala2, NMe-Phe4, Glyol5-enkephalin) produced overt sedation in all the age groups and also induced catalepsy which was particularly apparent in the 5- and 10-day-old animals. These compounds did not produce any signs of behavioural activation in the neonatal rats. In contrast, rat pups treated with the kappa-agonists U50,488H and PD 117,302 (1,10 mg/kg IP) exhibited marked hyperactivity with increases in wall-climbing and locomotion. Sedative effects of the highest dose of the kappa-agonists began to emerge, however, as the animals grew older, resulting in significant decreases in behaviours such as gnawing and grooming at 20 days of age. The kappa-agonist (+)-tifluadom (0.1-10 mg/kg), but not its corresponding (-)-isomer, produced an increase in activity in 5-day-old rats, thus extending the observations made with U50,488H and PD 117,302 and establishing the stereoselective nature of the response. The involvement of kappa-receptors in opioid-induced hyperactivity was further substantiated by using a variety of opioid antagonists. In this context, the increase in activity induced by U50,488H (10 mg/kg) in 5-day-old neonates was attenuated by naltrexone (1 mg/kg IP) but not by larger doses (10 mg/kg) of either M8008 (which has low affinity for kappa-receptors) or the selective delta-receptor antagonist ICI 174,864.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

In-vivo effects of ivermectin on Rhipicephalus appendiculatus: the influence of tick feeding patterns and drug pharmacokinetics.

Sublethal effects seen amongst Rhipicephalus appendiculatus feeding on ivermectin-treated rabbits were diverse and dependent both on drug dose, pharmacokinetics and tick feeding patterns: changes in drug formulation, the time of infestation relative to treatment, and the tick instar used, profoundly influenced acaricidal activity. Death was a sequel to paralysis only if tick feeding was interrupted for sufficient time to produce irreversible dehydration. Concurrent pharmacokinetic investigations revealed that, for the larvae of R. appendiculatus, the mean critical lethal dose of ivermectin imbibed over a 5-day engorgement period was 3500 micrograms/kg. This quantity of ivermectin was achieved in the blood-meals of larvae feeding on rabbits treated subcutaneously with a single dose of Ivomec injection (MSD)* greater than or equal to 800 micrograms/kg, provided infestation took place within 24 h of treatment. At lower drug doses, or if larval infestations were delayed for greater than 24 h post-treatment, the quantity of circulating ivermectin (and thus imbibed by the tick larvae) fell below 3500 micrograms/kg and an increasing percentage of larvae successfully engorged and detached. More than 90% of such larvae moulted to the nymphal stage. Nymphae and larvae exhibited similar susceptibility to ivermectin on treated rabbits which could be explained by similar feeding patterns. However, adult female and male ticks were markedly less susceptible and interpretation of ivermectin-induced effects was more complex.

Animals↗

PubMed1989

Exploring delta-receptor function using the selective opioid antagonist naltrindole.

Until recently the only pharmacological probes for delta-receptors have been peptide enkephalin analogues. These suffer from a number of limitations including high cost, partial agonist effects and a propensity for neurotoxicity. A stable non-peptide antagonist, naltrindole, has recently become available. We have explored its intrinsic actions and found that it attenuated swim stress-induced antinociception, a model for endogenous delta-receptor activation. Naltrindole may therefore be a useful alternative to presently available delta-receptor antagonists.

Animals↗

PubMed1989

Behavioural profiles of putative 5-hydroxytryptamine receptor agonists and antagonists in developing rats.

The effects of a variety of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on behaviour in 5- and 20-day old rat pups have been investigated. Increased locomotion and head-weaving responses were induced in both age groups by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin; 5-HT1A agonist); 5-MeODMT (5-methoxy-N,N-dimethyltryptamine; 5-HT1) and RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyrindin-4-yl)-1H-indole; 5-HT1B/5-5HT1A). The putative 5-HT1A-agonist LY165163 (1-2-(4-aminophenyl)ethyl 4-(3-trifluoromethylphenyl)piperazine) also produced hyperactivity in the developing pups. In contrast, locomotion was not affected by buspirone (5-HT1A); mCPP (1-(3-chlorophenyl)piperazine; 5-HT1B/5-HT1C) and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; 5-HT2) though buspirone produced a small increase in head-weaving at 5- and 20-days. The full 5-HT syndrome was induced in older animals (but not neonates) by both 8-OH-DPAT and 5-MeODMT. Large doses of buspirone, mCPP and DOI also produced signs of reciprocal forepaw treading and flattened body posture at 20-days. In addition, mCPP induced grooming and stereotyped mouthing, while DOI increased sniffing behaviour in the young rats. Catecholaminergic mechanisms were implicated in the head-weaving and locomotor responses to 8-OH-DPAT and RU 24969, following experiments with a number of monoamine receptor antagonists. Preliminary findings with (-)-pindolol, which was high affinity for 5-HT1-receptors, suggested that this subtype of receptor may play a role in hyperlocomotion induced by RU 24969.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1989

Ivermectin as a systemic insecticide.

Like many broad-spectrum drugs, the antiparasitic agent ivermectin is not equally effective in the treatment of all parasitic infestations. Predicting arthropod susceptibility relies not only on an understanding of insect and acarine biology, but also on an appreciation of the pharmacokinetic properties of the drug which can be profoundly influenced by host differences and pharmaceutical formulation. In this review, Helen Jackson attempts to explain the diverse number of ivermectin-induced effects observed among parasitic arthropods feeding on treated animals and aims to provide an overview of the current and future use of ivermectin in the systemic treatment and control of arthropod pests of livestock.

Journal Article↗

PubMed1989

Swim-stress-induced antinociception in young rats.

1. Opioid and non-opioid mechanisms have been implicated in the phenomenon of stress-induced antinociception in adult rodents. We have studied stress-induced antinociception in developing rats and characterized differences in the neurochemical basis of this effect in pre- and post-weanling animals. 2. Twenty and 25 day old rats were stressed using warm water (20 degrees C) swimming for 3 or 10 min periods and antinociception was assessed by the tail immersion test (50 degrees C). 3. A 3 min swim in 20 and 25 day old rats produced marked antinociception which was blocked by naloxone, Mr 1452, 16-methyl cyprenorphine and levallorphan but not Mr 1453 or N-methyl levallorphan. The delta-opioid receptor antagonist ICI 174,864 attenuated stress-induced antinociception in 25 day old rats but was without effect in 20 day old animals. 4. A 10 min swim in 25 day old rats produced antinociception which was non-opioid in nature. In contrast, antinociception was not observed in 20 day old rats after a 10 min swim-stress. 5. Pretreatment of animals with dexamethasone blocked 3 min swim-stress antinociception in 20 and 25 day old animals but had no effect on antinociception induced by a 10 min swim. 6. Swim-stress-induced antinociception can be observed in young rats and dissociated into opioid and non-opioid types dependent on the duration of swimming stress. The non-opioid type appears to develop more slowly and cannot be observed in preweanling rats. The opioid type is a predominantly mu-receptor phenomenon in preweanling animals but delta-receptor components are observable in postweanling rats.

Aging↗

PubMed1989

Perinatal lead exposure impairs opioid but not non-opioid stress-induced antinociception in developing rats.

1. The development of opioid systems has been shown to be sensitive to perinatal exposure to lead. We have studied the effects of such exposure on opioid and non-opioid mediated stress-induced antinociception in developing rats. 2. Lead was administered in the maternal drinking water from conception to postnatal day 14 at 300 and 1000 p.p.m. Twenty and 25 day old rats were subjected to swimming stress and antinociception measured using the tail immersion test. 3. A 3 min swim-stress induced an opioid-mediated antinociceptive response in 20 day old rats which was attenuated by 300 p.p.m. lead and by 1000 p.p.m. lead treatment in a dose-related manner. A 10 min swim-stress induced a non-opioid mediated antinociceptive response in 25 day old rats which was not antagonised by 300 or 1000 p.p.m. lead. 4. Naloxone antagonised the residual antinociception observed in 20 day old animals treated with 300 p.p.m. lead and had no effect on antinociception in control or lead-treated 25 day old rats. 5. Using a lead exposure model considered to represent subclinical lead toxicity in man, it was shown that perinatal lead exposure disrupts opioid but not non-opioid mediated stress antinociception.

Animals↗

PubMed1989

Effects of opioid agonists on urine production in neonatal rats.

The modulatory effects of opioids on urine production in adult rats have been well-documented. We report here the first investigation of the effects of these agents on urination in neonatal rats. The kappa-agonists U50,488H (1,10 mg kg-1) and (+)-tifluadom (10 mg kg-1) produced an increase in urine output in 10-day old pups whereas the (-)-isomer of tifluadom was ineffective in this model. The diuretic effects of the highest dose of U50,488H were attenuated by a 10 but not a 1 mg kg-1 dose of the opioid antagonist naltrexone. These findings suggest that kappa-agonists, as in adult animals, produce diuresis in neonates by activity at kappa-opioid receptors and also confirm the stereoselective nature of the response. The increase in urination produced by U50,488H (10 mg kg-1) was also reduced by the alpha-adrenoceptor antagonist phentolamine (1 mg kg -1), an observation which supports the hypothesis that kappa-agonists--in addition to their well-established inhibitory effects on the release of antidiuretic hormone--may increase urination via an adrenergic mechanism at the level of the adrenal medulla. The mu-opioid agonist morphine (0.1-10 mg kg-1), in contrast to its observed effects in older animals, did not produce antidiuresis in either normally-hydrated or water-loaded 10-day old rat pups. The results of this study therefore show that the stimulatory effects of kappa-agonists on urine production appear to be fully-functional at 10-days but the inhibitory effects of opioids on urination lag behind in development.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1986

Characterization of the effects of (+/-)-meptazinol, its individual enantiomers and N-methyl meptazinol on food consumption in the rat.

Both (+/-)-meptazinol (2 mg kg-1) and levorphanol (1 mg kg-1) produced hyperphagia over a 4 h period after intraperitoneal injection in free feeding rats during the daylight phase. The individual (+)- and (-)-enantiomers of meptazinol (2 mg kg-1 i.p.) induced comparable increases in cumulative food intake. N-methyl meptazinol (2-10 mg kg-1 i.p.), the quaternary analogue of meptazinol, produced no modification of food intake though it increased food consumption when injected intracerebroventricularly (10-100 micrograms per animal). Meptazinol and levorphanol hyperphagia was abolished by 1 mg kg-1 doses (i.p.) of the opioid antagonists naltrexone, naloxonazine and (-)-Mr 1452 but not by its (+)-enantiomer Mr 1453 which is not effective as an opioid antagonist. Intracerebroventricular administration of the delta-opioid antagonist ICI 154,129 (10 micrograms per animal) suppressed meptazinol but not levorphanol hyperphagia. It was concluded that meptazinol produces centrally mediated stereospecifically reversible hyperphagia through a mu-opioid receptor mechanism common to levorphanol, and also through delta-opioid receptor mechanism(s).

Animals↗

PubMed1985

Involvement of endogenous enkephalins in the feeding response to diazepam.

The effect of the delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) and the benzodiazepine diazepam on the food intake of non-deprived rats was investigated. Both compounds produced a significant increase in feeding. The hyperphagic response to DADLE (10 micrograms i.c.v.) and diazepam (1 mg/kg i.p.) was suppressed by concurrent treatment with the selective delta-opioid antagonist ICI 154,129 (10 micrograms i.c.v.). These findings add further support to the concept that endogenous enkephalins may be implicated in the stimulatory effects of benzodiazepines on ingestive behaviour.

Animals↗

PubMed1985

Hyperphagia induced by 2-deoxy-D-glucose in the presence of the delta-opioid antagonist ICI 174,864.

The effect of the selective delta-opioid antagonist ICI 174,864 (N,N-bisallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib=alpha-aminoisobutyric acid) on the hyperphagia induced by 2-deoxy-D-glucose (2-DG) was investigated in non-deprived rats. The increase in food intake produced by 2-DG (500 mg/kg i.p.) was not reduced by ICI 174,864 at a dose (3 micrograms/rat i.c.v.) which totally abolished the feeding response to the delta-agonist D-Ala2-D-Leu5-enkephalin (10 micrograms/rat i.c.v.). These findings suggest that the appetitive effects of 2-DG are not mediated by an enkephalinergic/delta-receptor system. They do not, however, preclude the possible involvement of endogenous opioids acting at other sub-types of opioid receptor in this glucoprivic ingestional response, which is suppressed by less specific opioid antagonists such as naloxone.

Animals↗

PubMed1985

Are delta-opioid receptors involved in the regulation of food and water intake?

The effect of the delta-opioid antagonists ICI 154,129 (1-100 micrograms, i.c.v.) and ICI 174,864 (1-100 micrograms, i.c.v.) and of the delta-agonist D-Ala2-D-Leu5-enkephalin (DADL; 1-10 micrograms, i.c.v.) on the intake of food and water of non-deprived rats was investigated. Animals treated with either ICI 154,129 or ICI 174,864 ate and drank significantly less than vehicle-treated controls over a 3 hr test period. The suppressant effects of these peptides on appetite were similar to those observed with the more commonly-used opioid antagonists, naltrexone and Mr 2266. In contrast, the delta-agonist DADL produced an increase in both the consumption of food and water in the 3 hr following administration of drug. The findings presented in this study lend further support to the hypothesis that an endogenous enkephalin/delta-receptor system may play a role in the tonic induction of ingestive behaviour.

Animals↗

PubMed1984

The involvement of mu- and kappa- but not delta-opioid receptors in the body weight gain of suckling rats.

The effects of the benzomorphan antagonist Mr 2266 and the selective delta-antagonist ICI 154,129 on the body weight gain of 6-day-old suckling rat pups was observed. Mr 2266 significantly reduced body weight gain in these animals, though ICI 154,129 had no affect on this variable. These findings suggest that mu- and kappa- but probably not delta-opioid receptors are involved in the regulation of ingestive behaviours in infant rats. The results are discussed in relation to the development of opioid-receptor subtypes in the neonatal rat brain.

Animals↗

PubMed1984

The role of opioid receptor sub-types in tifluadom-induced feeding.

There is now considerable evidence that opioid agonists and benzodiazepines increase food and water intake in a variety of animal species. The appetitive effects of the novel opioid-benzodiazepine tifluadom have been investigated. (+/-)-Tifluadom significantly increased food intake in freely-feeding rats. This stimulation of appetite was attributable principally to the activity of the (+)-isomer. Furthermore tifluadom-induced feeding was blocked by the opioid antagonists naloxone, naltrexone, Mr 1452 and Mr 2266 but not by the delta-opioid receptor antagonist ICI 154, 129, or by the benzodiazepine antagonist Ro 15-1788. These results suggest that tifluadom exerts its effect on food intake by interaction with opioid as opposed to benzodiazepine receptors and that this activity is mediated by kappa and/or mu- rather than delta-opioid receptor sub-types.

Animals↗