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I Kitchen

Publications and source records attributed to I Kitchen.

At least 73 records · Page 4Linked to original sources
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

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↗
PubMed1988

Comparative binding of mu and delta selective ligands in whole brain and pons/medulla homogenates from rat: affinity profiles of fentanyl derivatives.

The comparative binding characteristics of the mu opioid receptor selective ligand [3H]-[D-Ala2-MePhe4-glyol5]enkephalin [( 3H]-DAGO) and of the delta receptor ligand [3H]-[D-Pen2, D-Pen5]enkephalin[( 3H]-DPDPE) have been studied in homogenates of both whole brain and of pons/medulla regions from the rat. The receptor affinities of five 4-anilinopiperidine drugs (fentanyl derivatives) and of morphine have been determined by inhibition studies, using [3H]-DAGO and [3H]-DPDPE as markers of the mu and delta opioid binding sites, respectively. The concentration of delta opioid sites in pons/medulla was found to be approximately one third that of mu sites. The concentrations of both mu and delta sites in whole brain were similar to that of mu sites in pons/medulla. The rank order of affinities of the unlabelled drugs was dissimilar at the mu and delta sites. The most potent fentanyl derivatives exhibited negligible preference for the mu or delta sites, in contrast to the least potent compound, alfentanil which showed an extremely high mu-site selectivity.

Animals↗
PubMed1988

A new method for determination of in vivo pA2 using infusions of naloxone to steady-state blood concentrations.

A method is described for the measurement of pA2 in vivo for the opioid antagonist naloxone, infused to predicted steady-state blood concentrations in rats. The method has been applied to antagonism of the respiratory depressant effects of opioid agonists. The basis of the technique rests upon determination of the plasma clearance of the antagonist whence appropriate loading doses and zero order infusion rate constants are calculated. The predicted concentrations of naloxone were verified by direct plasma measurement. Using the infusion protocol pA2 determinations by Schild analysis were significantly different from those obtained by bolus injection. The approach described provides more accurate estimates of in vivo pA2 and could be applied to other antagonists, species, and biological responses, overcoming many of the problems inherent in the use of bolus antagonist dosing, which is currently widely employed.

Alfentanil↗
PubMed1988

Perinatal lead exposure alters the development of delta- but not mu-opioid receptors in rat brain.

1. Low level lead exposure has been shown to impair the development of opioid peptide levels in the brain, and to impair antinociceptive responses to opioid drugs. We have now studied the effects of lead exposure on the development of opioid receptors using ligand binding studies. 2. The ontogenesis of mu- and delta-opioid binding sites was studied using rat whole brain membranes and [3H]-[D-Ala2MePhe4-Gly-ol]enkephalin and [3H]-[D-Pen2,D-Pen5]enkephalin as binding ligands. Rats were exposed to lead during development by addition of lead acetate (at 100-1000 p.p.m.) to the maternal drinking water from conception to postnatal day 14. 3. Perinatal lead exposure had no significant effects on the binding affinity (KD) or binding capacity (Bmax) for the mu-opioid receptor measured at postnatal days 10, 21 and 30. Lead exposure (at 1000 p.p.m.) increased the KD for the delta-opioid receptor at postnatal days 15, 21, 35 and 50 but had no effect on the binding capacity. No indications of overt toxicity were observed and blood lead levels were in the ranges considered to represent subclinical lead toxicity in man. 4. The lack of effect of lead on mu-receptor binding contrasts with previously described impairment of antinociceptive effects of mu-agonists suggesting that the toxicity is not manifested at the mu-binding site. However, the delta-opioid receptor appears to be more sensitive to lead exposure and the persistent changes in delta-site affinity after cessation of lead exposure suggest irreversible damage in the production of the receptor protein.

Animals↗
PubMed1988

Dopamine receptor modulation of corticosterone secretion in neonatal and adult rats.

The effects of the dopamine agonist, pergolide, upon plasma corticosterone levels have been studied in 30 day old neonatal and adult rats. Dose-related elevations in corticosterone were observed at both ages and these elevations were blocked by the dopamine (D2) receptor antagonist spiperone. These studies demonstrate that dopaminergic neurochemical control of the hypothalamus-pituitary-adrenal axis exists in four week old rats in contrast to our previous studies which have shown opioid control to be absent at this age. It appears that neurochemical control of corticosterone is dissimilar in the neonate.

Aging↗
PubMed1988

Effects of proenkephalin products on rat cardiac and vascular tissue in-vitro.

The cardiovascular effects of the four proenkephalin products [Met]-enkephalin (ME), [Leu]-enkephalin (LE), [Met]-enkephalyl-arg6phe7 (MEAP) and [Met]-enkephalyl-arg6-gly7-leu8 (MEAGL) have been studied on the isolated spontaneously beating rat atria and the perfused rat mesentery in-vitro. All four peptides (at concentrations up to 10(-6)M and in the presence of peptidase inhibitors) had no direct effect on atrial rate or contractility and did not alter responses to noradrenaline or field stimulation. In addition, the peptides had no effect on the perfusion pressure of the mesentery and did not alter vasoconstrictor responses to noradrenaline. The results show that proenkephalin products are without direct or modulating effects on atrial muscle or mesenteric vasculature of the rat, and suggest that there is no endogenous opioid control in these tissues.

Animals↗
PubMed1988

Differences in the characteristics of opioid receptor binding in the rat and marmoset.

The density of mu and delta opioid binding sites in homogenates of rat and marmoset brain was determined using radiolabelled peptides with high receptor selectivity. In addition the affinity of mu and delta receptor binding of five drugs of the fentanyl series was measured. The ratio of mu: delta sites was similar within each species but the total receptor binding capacity in the rat was double that of the marmoset. The binding affinities for the delta site were dissimilar between the species and supports the hypothesis that the structure of this receptor shows phylogenetic differences. In contrast, mu site binding affinity was identical in rat and marmoset.

Animals↗
PubMed1987

Developmental responses to opioids reveals a lack of effect on stress-induced corticosterone levels in neonatal rats.

The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found that opioid modulation is absent in early postnatal development. Neonatal rats of either sex were injected with morphine (5-50 mg kg-1), fentanyl (10-100 micrograms kg-1), buprenorphine (0.1-30 mg kg-1) or naloxone (0.1-10 mg kg-1) and plasma corticosterone measured fluorimetrically 15 or 20 min later. In addition naloxone reversibility studies (1 mg kg-1, co-administered) were carried out for the opioid agonists. In adult rats, elevations in plasma corticosterone caused by injection stress were potentiated by morphine, fentanyl and buprenorphine. In neonates, though injection stress-induced rises in plasma corticosterone were absent at 10 days, elevations were observed at 21 days and later. However, significant potentiation of this corticosterone response by fentanyl was absent at 21 days and at later ages (30 and 40 days) for morphine and buprenorphine. The potentiating effect of all three agonists did not become fully effective until day 45. In addition, in animals acclimatized to injection stress by 7 day injection pretreatment, fentanyl did not significantly alter corticosterone levels in 30 day old neonates. High doses of naloxone (10 mg kg-1) significantly increased the corticosterone response to injection stress in adult rats but this effect was absent in 30 day old animals. A dose of naloxone (I mg kg-') which had no significant effect on the corticosterone response inhibited the effects of morphine, fentanyl and buprenorphine in 45 day old and adult rats. 5 This late development of opioid action is unusual in comparison with the maturation of endogenous peptides, receptors and antinociceptive responses and suggests that alternative mechanisms may be involved in stress-control in the neonate.

Aging↗
PubMed1986

Di-isopropylfluorophosphate induced antinociception and its interactions with opioid drugs in the rat.

The irreversible anticholinesterase, di-isopropylfluorophosphate (DFP), was shown to be antinociceptive in the paw pressure test in rats only at doses where animals exhibited marked signs of anticholinesterase poisoning. At sub-antinociceptive doses DFP potentiated the opioid drugs fentanyl and alfentanil but failed to alter morphine antinociception. These interactions differ from our previous studies using the hot plate test in mice and suggest that opioid/cholinergic interactions are species and test dependent.

Alfentanil↗
PubMed1986

Ontogenesis of delta-opioid receptors in rat brain using [3H][D-Pen2,D-Pen5]enkephalin as a binding ligand.

The ontogenesis of delta-opioid receptors has been studied in the postnatal period up to day 50 using the highly selective delta-site ligand [3H][D-Pen2,D-Pen5]enkephalin ([3H]DPDPE) in binding studies. Analyses of saturation curves revealed marked increases in binding capacities between the second and fourth postnatal week with little change in affinity. In contrast to findings with [3H][D-Ala2,D-Leu5]enkephalin binding could not be detected before postnatal day 10 which may be associated with the low affinity and specific activity of DPDPE. A low specific binding for [3H]DPDPE poses methodological problems in the use of this ligand for ontogenic studies.

Animals↗
PubMed1986

Ontogeny of catecholamine and GABA levels in rat brain: lack of effect of perinatal lead exposure.

In this study we report the ontogeny of noradrenaline, adrenaline, dopamine, and gamma-aminobutyric acid (GABA) in the rat striatum and the effect of perinatal exposure to low levels of lead. Lead administered in the maternal drinking water (100, 300 and 1000 ppm) from conception to weaning had no effect on the ontogeny of catecholamines. There was a 50% decrease in the levels of GABA at 10 days in rats exposed to the highest dose of lead, but no other changes were observed in lead-exposed rats at 21 and 30 days of age. These results contrast with our previously reported decrease in the levels of striatal proenkephalin products in lead-exposed rats, and suggest that this inhibitory effect of lead does not represent a generalised neurochemical toxicity.

Administration, Oral↗