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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 37 records · Page 2Linked to original sources
PubMed1995

5-HT3 receptor antagonism by anpirtoline, a mixed 5-HT1 receptor agonist/5-HT3 receptor antagonist.

1. The aim of this study was to provide evidence that anpirtoline, which is an agonist at 5-HT1B and 5-HT1D receptors and also displays submicromolar affinity for 5-HT1A recognition sites, in addition, acts as an antagonist at 5-HT3 receptors. 2. In radioligand binding studies on rat brain cortical membranes, anpirtoline inhibited specific binding of [3H]-(S)-zacopride to 5-HT3 receptor recognition sites (pKi: 7.53). 3. In N1E-115 neuroblastoma cells in which [14C]-guanidinium was used as a tool to measure cation influx through the 5-HT3 receptor channel, the 5-HT-induced influx was concentration-dependently inhibited by anpirtoline. In this respect, anpirtoline mimicked other 5-HT3 receptor antagonists; the rank order of potency was ondansetron > anpirtoline > metoclopramide. 4. The concentration-response curve for 5-HT as a stimulator of [14C]-guanidinium influx was shifted to the right by anpirtoline (apparent pA2: 7.78). 5. In urethane-anaesthetized rats, anpirtoline inhibited (at lower potency than zacopride and tropisetron) the 5-HT- or phenylbiguanide-induced bradycardia (Bezold-Jarisch reflex), but did not induce this reflex by itself. 6. Intravenous infusion of cisplatin in the domestic pig caused a consistent emetic response which was antagonized by anpirtoline. 7. It is concluded that anpirtoline, which was previously characterized as a 5-HT1 receptor agonist also proved to be a 5-HT3 receptor antagonist in several experimental models and, hence, exhibits a unique pattern of properties at different 5-HT receptors.

Animals↗
PubMed1995

[Cerebral venous thromboses: study of the course].

The management of patients with presumed cerebral venous thrombosis has been recently modified by magnetic resonance imaging and evidence that heparin decreases mortality and morbidity. No large consecutive series of patients with cerebral venous thrombosis has been reported since then. The aim of our study was to determine the prognosis factors of patients with cerebral venous thrombosis. Demographic, clinical and radiological characteristics were recorded in a homogeneous series of 18 consecutive patients with cerebral venous thrombosis collected over a 31-month period. All patients were treated by heparin at the acute stage. We found no difference in demographic, clinical and radiological characteristics of the patients according to the 1-month and 6-month outcome. We only found a tendency towards a better 1-month outcome in younger patients (p = 0.06) and in patients with an isolated intracranial hypertension (2p = 0.06). A long therapeutic delay might be a factor of poor prognosis which might be hidden by a better spontaneous outcome in patients with isolated intracranial hypertension in whom the diagnostic delay is longer. A multicentric study allowing a multivariate analysis may therefore be useful to identify prognosis factors in patients with cerebral venous thrombosis.

Adolescent↗
PubMed1995

Characterization of a progesterone-binding, three-domain antibody fragment (VH/K) expressed in Escherichia coli.

The heavy chain variable region (VH) and the kappa light chain of the anti-progesterone monoclonal antibody (mAb) DB3, have been expressed as a single-chain three-domain polypeptide, designated VH/K, and secreted into the periplasmic space of Escherichia coli (E. coli). The linker sequence was derived from the VH-CH1 elbow region. The C kappa domain provides a sensitive detection tail for Western blotting and enzyme-linked immunosorbent assay (ELISA). Periplasmic extracts of transformed E. coli contained material that bound progesterone and related steroids with similar specificity and affinity to DB3, and displayed the DB3 idiotype and kappa chain epitopes. Reference to the crystal structure of DB3 suggests that all the characteristics of the combining site interaction with steroids are retained in the bacterially expressed material. Western blotting demonstrated material with a molecular weight equivalent to three domains after reduction, but six domains in the unreduced state, suggesting that the VH/K polypeptide is assembled in the periplasm as a disulphide-bridged dimer. The VH/K construct provides a novel route to expression of antibody combining sites in E. coli for antibody engineering.

Animals↗
PubMed1995

Are postsynaptic 5-HT1A receptors involved in the anxiolytic effects of 5-HT1A receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat?

Previous studies have shown that injection of 5-hydroxytryptamine (serotonin) receptor agonists in the dorsal raphe nucleus (DRN) to stimulate somatodendritic 5-HT1A autoreceptors or in the hippocampus to stimulate postsynaptic 5-HT1A receptors, induces anxiolytic-like effects in the rat. The mechanisms triggered by the latter treatment were investigated by measuring both the electrical activity of serotonergic DRN neurons and the anxiolytic response in rats receiving injections with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) or ipsapirone into the dorsal hippocampus. Anxiety-related behavior was estimated by recording the time of ultrasonic vocalization (USV) due to electric foot shocks under standardized conditions. Intrahippocampal application of 8-OH-DPAT or ipsapirone produced a dose-dependent inhibition of the firing of serotonergic DRN neurons and of the shock-induced USV response. However, the range of efficient doses of 8-OH-DPAT via the intrahippocampal route (1-10 micrograms/rat) was larger than that using the i.v. route of injection (0.15-2.5 micrograms/rat). Furthermore, maximal inhibition of the firing of DRN serotonergic neurons occurred earlier when 8-OH-DPAT was injected i.v. (within 1-2 min) than when it was injected into the dorsal hippocampus (within 5 min). Interestingly, the injection of 8-OH-DPAT into the striatum, where 5-HT1A receptors are hardly detectable, or a lateral ventricle, also yielded dose-dependent reduction in both the firing rate of serotonergic DRN neurons and the USV response. Finally, local lesion with ibotenic acid to eliminate postsynaptic 5-HT1A receptors did not alter the inhibitory effects of intrahippocampal application of 8-OH-DPAT on the firing of serotonergic DRN neurons and the USV response. These data indicated that postsynaptic 5-HT1A receptors were not responsible for the inhibitory effects of 8-OH-DPAT and ipsapirone injected in forebrain areas on the electrical activity of serotonergic neurons and the USV response in rats. As shown by the autoradiographic labeling by [3H]8-OH-DPAT at distance from its injection site in the dorsal hippocampus, the diffusion of 5-HT1A receptor agonists (from injected areas in the forebrain to the DRN where they directly inhibit the electrical activity of serotonergic neurons) more likely accounted for their anxiolytic-like effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Neointimal thickening after balloon denudation is enhanced by aldosterone and inhibited by spironolactone, and aldosterone antagonist.

OBJECTIVE: The aim was to examine the effects of aldosterone and of an aldosterone antagonist, spironolactone, on neointimal thickening in a rabbit model of balloon injury. METHODS: Eighteen rabbits underwent aortic and iliac balloon injury and were randomised to subcutaneous infusion of aldosterone (70 micrograms.kg-1.d-1) or vehicle solution for 28 d. Eighteen other rabbits were randomised to receive daily subcutaneous injections of spironolactone (50 mg.kg-1.d-1) or of vehicle for 7 d before injury and for 28 d after the procedure. All animals were then killed just after measurement of plasma renin activity and of arterial pressure. Vessels were fixed and five cross sections were analysed per rabbit (three aortic; two from iliac artery). Mean values of neointimal area and of the neointimal area/medial area ratio were calculated. RESULTS: Aldosterone treatment was associated with a decrease in renin activity and a non-significant increase in mean arterial pressure. Aldosterone significantly augmented the neointimal thickening in the iliac artery [0.42(SEM 0.07) v 0.24(0.03) mm2, P < 0.05] but not in the aorta [0.63(0.08) v 0.59(0.12) mm2, NS]. Spironolactone significantly inhibited intimal thickening, both in the iliac artery [0.09(0.02) v 0.29(0.01) mm2, P < 0.001] and in the aorta [0.31(0.03) v 0.59(0.06) mm2, P < 0.001]. Spironolactone administration was associated with an increase in renin activity and a decrease in mean arterial blood pressure. CONCLUSIONS: Aldosterone administration enhances neointimal thickening after injury and spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal thickening in the same model. This suggests a role for aldosterone in the pathophysiology of neointimal proliferation after balloon injury and for aldosterone antagonists in its prevention.

Aldosterone↗
PubMed1994

Selective in vivo labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse.

The novel selective 5-HT1A receptor antagonist radioligand [3H]WAY 100635 ([O-methyl-3H]N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- pyridyl)cyclohexane-carboxamide) was injected i.v. to mice in an attempt to label in vivo central 5-HT1A receptors. Although 5 min after the i.v. injection of [3H]WAY 100635 (4-7.6 muCi per mouse) the amount of tritium found in the whole brain only accounted for 1.5-1.8% of the injected radioactivity, regional differences in 3H accumulation already corresponded to those of 5-HT1A receptor density. Optimal data were obtained 1 h after [3H]WAY 100635 injection as the distribution of 3H in brain was exactly that of 5-HT1A receptor binding sites in mouse brain sections labelled in vitro with [3H]WAY 100635. In particular, high level of labelling was found in the lateral septum, gyrus dentatus and CA1 area of Ammon's horn in the hippocampus, dorsal raphe nucleus and entorhinal cortex. No labelling was found in he substantia nigra, and 3H accumulated in the cerebellum represented only 12-14% of that found in the hippocampus. Pretreatment with various drugs indicated that only 5-HT1A receptor ligands were able to decrease the accumulation of 3H in all the brain areas examined except in the cerebellum. Assuming that only non-specific binding took place in the latter structure, it was possible to calculate the ID50 values of 5-HT1A receptor agonists (8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), S 14506 (1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl+ ++)piperazine) and S 20499 ((+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]butyl-8- azaspiro-(4,5)-decane-7,9-dione)) and antagonists (spiperone, (-)-tertatolol, (+)-WAY 100135 (N-tert-butyl-3,4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl- propanamide)) as inhibitors of 3H accumulation in the hippocampus of [3H]WAY 100635-injected mice. Comparison of these values with the in vitro affinity of the same ligands for hippocampal 5-HT1A receptors revealed marked variations in the capacity of 5-HT1A receptor agonists and antagonists to reach the brain when injected via the subcutaneous route in mice.

Animals↗
PubMed1994

Neurotrophic effects of ipsapirone and other 5-HT1A receptor agonists on septal cholinergic neurons in culture.

Repeated treatment of primary cultures of fetal rat septal neurons with 5-HT1A receptor agonists (8-OH-DPAT, ipsapirone, gepirone and buspirone) increased choline acetyltransferase activity after 6-7 days in culture. This effect was optimal with ipsapirone (+ 50-80% at 1 microM of the agonist), and could be prevented by potent 5-HT1A receptor antagonists such as (-)-tertatolol and (+)-WAY 100135. Under conditions where they completely suppressed the stimulatory effect of NGF on choline acetyltransferase in these cultures, specific anti-NGF antibodies did not alter the stimulatory effect of ipsapirone, suggesting that a possible release of NGF from some septal cells did not account for the effect of 5-HT1A receptor stimulation. Autoradiographic investigations with [3H]8-OH-DPAT as radioligand and immunocytochemistry with specific anti-choline acetyltransferase antibodies and anti-rat 5-HT1A receptor antibodies showed that 5-HT1A receptors were expressed on septal neurons in culture, notably on the cholinergic neurons identified by their positive staining with anti-choline acetyltransferase antibodies. Detailed morphometrical analysis by computer-assisted imaging revealed that repeated exposure to ipsapirone (1 microM for 7 days) did not influence the survival of cholinergic as well as non-cholinergic neurons, but specifically altered the neuritic tree (i.e. the total length of neurites and the number of branching points) of cholinergic neurons only. These data suggest that under in vitro conditions ipsapirone and other 5-HT1A receptor agonists may exert a direct trophic action on septal cholinergic neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Mu and delta opioid receptors mediate opposite modulations by morphine of the spinal release of cholecystokinin-like material.

The possible modulations by morphine and various opioids of the spinal release of cholecystokinin-like material (CCKLM) evoked by 30 mM K+ was studied in vitro, using slices of the dorsal part of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Addition of the mu agonist, DAGO (0.1-10 microM), to the perfusing fluid produced a concentration-dependent decrease in the peptide release, which could be prevented by the preferential mu antagonist, naloxone. Complex modulations were induced by the delta agonist, DTLET, as this drug inhibited CCKLM release when added at 10 nM-3 microM to the perfusing fluid, but enhanced it at 10 microM. Both effects were preventable by the delta antagonists naltrindole and ICI 154129, suggesting that delta receptors, possibly of different subtypes, mediated the inhibition and stimulation by DTLET. Morphine also exerted a biphasic effect, as the alkaloid decreased CCKLM release at 0.01-0.1 microM and enhanced it at 10 microM. Morphine-induced inhibition was preventable by naloxone, whereas its stimulatory effect could be blocked by naltrindole and ICI 154129. Although inactive on its own on CCKLM release, the selective kappa 1 agonist U 50488H (1 microM) prevented the inhibitory effects of both DAGO (10 microM) and morphine (0.1 microM), suggesting the existence of interactions between kappa 1 and mu receptors within the dorsal zone of the rat spinal cord. These data indicate that low concentrations of morphine exert an inhibitory influence on spinal CCKergic neurons that depends on the stimulation of mu opioid receptors. The excitatory influence of 10 microM morphine likely results from the simultaneous stimulation of mu, delta and kappa receptors, as the inhibitory effect of mu receptor stimulation can be masked by that of kappa 1 receptors, allowing only the expression of a delta-dependent excitatory effect similar to that induced by 10 microM DTLET.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Postnatal development and localization of 5-HT1A receptor mRNA in rat forebrain and cerebellum.

The localization of the rat brain 5-HT1A receptor mRNA was analyzed by RNAse mapping and in situ hybridization during postnatal development, particularly in the cerebellum. The regional distribution of 5-HT1A mRNA during the first 2 postnatal weeks was different from that found in adults. In some areas of the immature brain (hippocampus, cerebral cortex), 5-HT1A mRNA was found in lower density than in the adult brain. In contrast, high concentrations of the transcript were present in other brain structures only during the first days after birth. Thus, in the cerebellum, the density of 5-HT1A mRNA decreased markedly from day 2 to day 9 after birth and could hardly be detected in the adult animal. The localization of the mRNA in the molecular/Purkinje cell layer of the immature cerebellum agreed with that of the 5-HT1A receptor protein visualized by immunocytochemistry and was consistent with the hypothesis that Purkinje cells express this receptor.

Animals↗
PubMed1994

Neuronal localization of 5-HT1A receptor mRNA and protein in rat embryonic brain stem cultures.

The aim of the present work was to study the cellular localization of 5-HT1A receptor protein and mRNA in rat embryonic brain cultures. Primary cultures of the whole brain from rat fetuses at embryonic day (ED) 12 and of the brain stem at ED 14-ED 16 were stained with specific anti-5-HT1A receptor antibodies or a 40-mer biotin-labelled deoxyoligonucleotide complementary to the 5-HT1A receptor mRNA. The use of a biotinylated probe allowed the morphology of the cells to be preserved. 5-HT1A receptor mRNA was already detected in primary cultures from the brain of ED 12 embryos whereas the receptor protein first appeared two days later, at ED 14. Both 5-HT1A receptor mRNA and protein were found within neuron-like cells (labelled with antibodies against neuron specific enolase, microtubule-associated protein 2 or aromatic L-amino acid decarboxylase) but not in glial cells (specifically labelled with antibodies against glial fibrillary acidic protein, myelin basic protein or carbonic anhydrase II). Double staining with the 5-HT1A receptor mRNA probe and anti-5-HT antibodies suggests that 5-HT1A (auto)receptors are expressed by serotoninergic neurons during early ontogenesis.

Animals↗
PubMed1994

Interactions of lesopitron (E-4424) with central 5-HT1A receptors: in vitro and in vivo studies in the rat.

Previous studies have shown that the 5-HT1A receptor ligand, lesopitron (E-4424, 2-[4-[4-(4-chloro-1-pyrazolyl)butyl]-1-piperazinyl]pyrimidine), exerts potent anxiolytic-like effects in rodents and monkeys (Costall et al., 1992, J. Pharmacol. Exp. Ther. 262, 90). In an attempt to determine whether these effects are really mediated through the interaction of lesopitron with central 5-HT1A receptors, we investigated the agonistic and/or antagonistic nature of this interaction under in vitro and in vivo conditions in the rat. In vitro binding and autoradiographic studies with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and [3H]lesopitron as radioligands confirmed that lesopitron binds to 5-HT1A receptors in the rat brain with a relatively high affinity (pKi = 7.35). As expected of a full agonist at postsynaptic 5-HT1A receptors, lesopitron (IC50 = 125 nM) inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes to the same extent as 5-HT, and this effect was preventable by potent 5-HT1A receptor antagonists such as (-)-tertatolol, (-)-propranolol and N-tert-butyl-3,4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl- propanamide ((+)-WAY 100135). As previously shown for agonists acting at the somato-dendritic 5-HT1A autoreceptors in the dorsal raphe nucleus, lesopitron inhibited the firing of serotoninergic neurons both in vitro (in brainstem slices, IC50 = 120 nM) and in vivo (in chloral hydrate-anaesthetized rats, ID50 = 35 micrograms/kg i.v.), and this effect was preventable by (-)-tertatolol. Interestingly, the inhibition of the discharge due to lesopitron lasted for only a few minutes both in vitro and in vivo whereas the anxiolytic-like properties of this drug lasted for hours after a single injection in mice (Costall et al., 1992). In addition, the doses required for the stimulation of pre- and postsynaptic 5-HT1A receptors were markedly higher than those producing significant anxiolytic-like effects in rodents (Costall et al., 1992). It is therefore unlikely that the anxiolytic-like properties of lesopitron involve its stimulatory action at central 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Effect of balloon inflation in angiographically normal coronary segments during coronary angioscopy: a quantitative angiographic study.

Visualization of coronary stenoses by coronary angioscopy is facilitated by inflating an occlusive cuff located near the distal end of the device to temporarily interrupt blood flow. In animal models, this procedure induces substantial endothelial denudation. Experimental studies show that endothelial denudation may lead to neointimal hyperplasia at the denuded site. This study was designed to determine whether angioscopy was associated with significant changes in lumen diameter at the site of cuff inflation. We studied 52 consecutive patients undergoing coronary angioscopy. We measured with use of quantitative edge-detection angiography [computer-assisted evaluation of stenosis and restenosis (CAESAR) system] the mean and minimal lumen diameters at the site of cuff inflation localized by filming the inflated cuff during angioscopy and at control non-instrumented segments on angiograms performed before angioscopy, after angioscopy, and at 6 months follow-up. Follow-up angiograms were performed in 80% of eligible patients. At follow-up, the mean (3.22 +/- 0.54 mm) and minimal (2.76 +/- 0.58 mm) diameters of the segment exposed to the inflated cuff were not significantly different from the equivalent values (3.22 +/- 0.58 and 2.75 +/- 0.61 mm) before angioscopy. No significant changes occurred in the mean or minimal diameters of the control segments over the same period. The late change (follow-up minus pre-angioscopy) in mean lumen diameter at the cuff inflation site (-0.005 +/- 0.18 mm) was not significantly different from that at the control site (0.004 +/- 0.20 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Differential effects of the novel analgesic, S 12813-4, on the spinal release of substance P- and calcitonin gene-related peptide-like materials in the rat.

The possible inhibitory control by the novel analgesic S 12813-4 (3-(2-(4-phenylpiperazine-1-yl)-ethyl)-2-oxo-2,3- dihydrooxazolo(b)pyridine) of spinal neurones containing substance P (SP) and/or calcitonin gene-related peptide (CGRP) was assessed in vitro and in vivo in the rat. S 12813-4 (10 nM-0.1 mM) did not affect the spinal release of CGRP-like material (CGRPLM) but inhibited in a concentration dependent manner the K(+)-evoked overflow of SP-like material (SPLM) from slices of the dorsal half of the rat lumbar enlargement. The inhibitory effect of 10 microM S 12813-4 on SPLM release was not additive with that of Na (0.1 mM), and could be prevented by the alpha 2-adrenoceptor antagonist idazoxan (10 microM). Similarly, idazoxan (10 microM) suppressed the inhibition by intrathecally administered S 12813-4 (10 microM) of the spinal outflow of SPLM in halothane anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. These data suggest that the analgesic effect of S 12813-4 might involve some alpha 2-adrenoreceptor-mediated control of SPLM release within the spinal cord. Whether this control concerns SP-containing primary afferent fibres (presynaptic inhibition) or SP-containing interneurones and/or bulbo-spinal SP-ergic pathways (postsynaptic inhibition) deserves further investigations.

Adrenergic alpha-Antagonists↗
PubMed1994

Effects of acute and chronic treatment with amoxapine and cericlamine on the sleep-wakefulness cycle in the rat.

Antidepressant drugs, such as the tricyclics and the serotonin reuptake inhibitors, are well known to decrease paradoxical sleep and occasionally increase slow wave sleep in human and in animals. In order to examine whether amoxapine (a mixed NA reuptake blocker and 5-HT2/5-HT3 antagonist) and cericlamine (a selective 5-HT reuptake inhibitor) exert the same effect in rats, and to investigate the possible relationships between sleep, the action of antidepressants and the serotoninergic system, the effects of these two different drugs were examined under acute and chronic conditions. Acutely, amoxapine (1, 5 and 10 mg/kg; i.p.) and cericlamine (1, 8, 16 and 32 mg/kg; i.p.) decreased paradoxical sleep and increased deep slow wave sleep especially when they were given at a low dose. When administered for 14 days, amoxapine induced a sustained decrease of paradoxical sleep during the whole treatment, while some tolerance was observed with regard to the inhibitory effect of cericlamine on this state of sleep. In addition, a rebound of paradoxical sleep occurred on the first day of cericlamine withdrawal. Thus, amoxapine and cericlamine exerted the same effects on the states of vigilance in the rat as do other antidepressants. The effects of cericlamine on sleep probably reflect its blocking action on 5-HT uptake, whereas the more complex effects of amoxapine might involve its 5-HT2/5-HT3 antagonist properties.

Amoxapine↗
PubMed1994

Effects of 5-HT1A receptor ligands on a safety signal withdrawal procedure of conflict in the rat.

The present study evaluated in the rat the ability of various 5-HT1A receptor agonists to exert an "anxiolytic-like" release of the suppression of lever pressing for food induced by the withdrawal of a conditioned signal for safety without presentation of a conditioned signal for punishment. During the period associated with the safety signal withdrawal (Saf.CS-/Pun.CS-), control rats exhibited a typical pattern of responding with an initial strong blockade of responding that lessened over the period as presses were rewarded and shocks omitted. The 5-HT1A receptor partial agonists buspirone (0.125-0.5 mg/kg) and 8-(2-[2,3-dihydro-1,4-benzodioxin-2-yl- methylamino]ethyl)-8-azaspiro[4,5]decane-7,9-dione methyl sulfonate (MDL 73005EF; 0.5-2 mg/kg) and the full agonist (+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]-butyl-8- azaspiro[4,5]decane-7,9-dione (S 20499; 0.125-1 mg/kg) produced a robust and dose-related release of pressing during the Saf.CS-/Pun.CS- period. This effect was less marked with ipsapirone (0.125-1 mg/kg). Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.06-0.25 mg/kg), a full agonist, was completely inactive and did not prevent MDL 73005EF (1-2 mg/kg) or diazepam (0.125 mg/kg) from releasing the suppressed behavior. The specific 5-HT1A antagonist (+)-N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpr opa namide [(+)-WAY 100135; 0.25-8 mg/kg] and the beta-adrenoceptor/5-HT1A antagonist (-)-tertatolol (2-8 mg/kg) did not modify the behavioral blockade, nor did (+)-WAY 100135 (2-4 mg/kg) reduce the ability of buspirone (0.25 mg/kg) to enhance responding during the Saf.CS-/Pun.CS- period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Morphine reduces the release of met-enkephalin-like material from the rat spinal cord in vivo by acting at delta opioid receptors.

The modulation by morphine of the spinal release of met-enkephalin-like material (MELM) was investigated in anaesthetized rats whose intrathecal space was perfused with an artificial CSF (ACSF). Morphine (10 microM in the ACSF), as well as a mu- (DAGO, 10 microM) or delta opioid receptor agonist (DTLET, 10 microM), significantly decreased the outflow of MELM. The effects of morphine and DTLET were prevented by the delta antagonist, naltrindole (10 microM), but not by naloxone (10 microM). Conversely, naloxone, but not naltrindole, prevented the inhibitory effect of DAGO. Although neither the kappa 1 agonist, U 50488H (10 microM), nor the kappa 1 antagonist, norbinaltorphimine (10 microM), exerted on their own any significant effect, norbinaltorphimine enhanced the inhibitory action of morphine. In contrast to the inhibition induced by morphine (with or without naloxone) which was preventable by 10 microM naltrindole, the inhibition of MELM release by morphine plus norbinaltorphimine was only partly reduced by naltrindole. Thus, concomitant stimulation of mu, delta and kappa 1 receptors might account for the apparent delta opioid receptor-dependent inhibition of MELM release by morphine. Indeed, its potential inhibitory effect through the stimulation of mu receptors (normally prevented by the concomitant stimulation of kappa 1 receptors) becomes efficient only when kappa 1 receptors are blocked.

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