共查询到8条相似文献,搜索用时 15 毫秒
1.
Delta-9-tetrahydrocannabinol (THC), the main psychoactive principle of cannabis, has been shown to attenuate the exhibition of signs of the quasi-morphine withdrawal syndrome in rats. Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect. Cannabidiol was without effect at the dosage levels used. The efficacy of these cannabinoids and the potency differences recorded in this study are in accord with their effects on other behaviours, both in experimental animals and in man. The activity of THC and CBN was not affected by the narcotic antagonist, naloxone. 相似文献
2.
Methylxanthines produce a quasi-morphine withdrawal syndrome (QMWS) in opiate naive rats. Additionally, methylxanthine-induced suppression of conditioned behavior in rats is reversed by the alpha2 adrenergic agonist clonidine which also attenuates true opiate withdrawal and the QMWS. Therefore, the operant behavioral effect of 3-isobutyl-1-methylxanthine (IBMX) provide a model with which to study mechanisms involved in the expression of opiate withdrawal. In order to examine the role of serotonin (5-HT) in the rate-decreasing effects of IMBX on operant behavior, the 5-HT precursor 5-hydroxytryptophan, and 5-HT reuptake blocker fluoxetine were administered in combination with IBMX to rats performing a, fixed-ratio 30 operant for food reinforcement. Both drugs failed to reverse the behavioral suppression caused by relatively low doses of IBMX, suggesting that elevated 5-HT neurotransmission contributes to, rather than attenuates, the QMWS. The relatively selective 5-HT2 antagonists mianserin and pirenperone blocked the IBMX-induced suppression, whereas the classic 5-HT antagonist methysergide had no effect. The results indicate that the operant behavioral effects of IBMX and possibly the QMWS may be mediated by serotonergic mechanisms. 相似文献
3.
Guillaume Lucas Norbert Bonhomme Philippe De Deurwaerdère Michel Le Moal U. Spampinato 《Psychopharmacology》1997,131(1):57-63
In this study, both catalepsy and changes in extracellular levels of striatal dopamine (DA) and dihydroxyphenyl acetic acid
(DOPAC) induced by the typical neuroleptic haloperidol (HAL) were simultaneously assessed, using intracerebral microdialysis
in freely moving rats, in the presence of either the 5-HT1A agonist 8-OH-DPAT or the 5-HT2A/C antagonist ritanserin. HAL (1 mg/kg, SC) elicited a strong cataleptic state, reaching its maximal intensity (about 240 s)
2 h after the drug administration. This effect was paralleled by a long-lasting enhancement of striatal DA and DOPAC extracellular
levels, reaching 230 and 350% of basal values, respectively. 8-OH-DPAT (0.1 mg/kg, SC) given 2.5 h after, and ritanserin (0.63
and 1.25 mg/kg, IP), given 15 min prior to HAL, significantly reduced the neuroleptic-induced catalepsy. However, both 5-HT
agents failed to modify basal DA and DOPAC striatal outflow as well as the stimulatory effect of HAL on these parameters.
It can thus be concluded that the anticataleptic effect of these compounds is not related to an alteration of DA release within
the striatum.
Received: 29 August 1996/Final version: 25 November 1996 相似文献
4.
Tryptamine produced a concentration-related inhibition of potassium-evoked release of tritium from slices of rat hypothalamus preloaded with 3H-serotonin. This effect of tryptamine was blocked by a series of serotonin antagonists with a relative order of potency which suggested that tryptamine was acting on a post-junctional serotonin receptor. However, the response to tryptamine was also blocked by tetrodotoxin, indicating that tryptamine may be acting indirectly via the release of a second neurotransmitter. The finding that physostigmine enhanced, whilst atropine antagonised the effect of tryptamine suggests that the second neurotransmitter may be acetylcholine. This possibility is discussed. 相似文献
5.
Rationale Diminished interest or pleasure in rewarding stimuli is an affective symptom of amphetamine withdrawal and a core symptom of depression. An operational measure of this symptom is elevation of brain stimulation reward thresholds during drug withdrawal. Data indicated that increasing serotonin neurotransmission by co-administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the serotonin-1A receptor antagonist p-MPPI reversed reward deficits observed during drug withdrawal (Harrison et al. 2001).Objectives We tested the hypothesis that increased serotonergic and noradrenergic neurotransmission, using the SSRI paroxetine which also inhibits noradrenaline reuptake, would alleviate affective aspects of amphetamine withdrawal.Methods A discrete-trial, current-threshold, self-stimulation procedure was used to assess brain reward function. The effects of paroxetine and p-MPPI alone and in combination were assessed in non-drug-withdrawing animals. We assessed also the effects of paroxetine and p-MPPI alone and in combination on reward deficits associated with amphetamine withdrawal.Results Paroxetine or p-MPPI alone had no effect on thresholds, while the co-administration of p-MPPI (3 mg/kg) and paroxetine (1.25 mg/kg) elevated thresholds in non-withdrawing rats. Amphetamine withdrawal resulted in threshold elevations. The co-administration of p-MPPI and paroxetine reduced the duration of amphetamine-withdrawal-induced reward deficits.Conclusions Increased serotonergic and noradrenergic neurotransmission decreased reward function in non-withdrawing rats, while the same treatment reversed reward deficits associated with amphetamine withdrawal. Considering that paroxetine acts on both the serotonin and noradrenaline transporter, these results indicate that the affective symptoms of amphetamine withdrawal, similar to non-drug-induced depressions, may be, in part, mediated through reduced serotonergic and noradrenergic neurotransmission. 相似文献
6.
Zopf DA das Neves LA Nikula KJ Huang J Senese PB Gralinski MR 《European journal of pharmacology》2011,(1):195-203
Pulmonary arterial hypertension (PAH) is a chronic disease characterized by sustained elevation of pulmonary arterial pressure that leads to right ventricle failure and death. Pulmonary resistance arterioles in PAH undergo progressive narrowing and/or occlusion. Currently approved therapies for PAH are directed primarily at relief of symptoms by interfering with vasoconstrictive signals, but do not halt the microvascular cytoproliferative process. In this study we show that C-122 (2-amino-N-(2-{4-[3-(2-trifluoromethyl-phenothiazin-10-yl)-propyl]-piperazin-1-yl}-ethyl)-acetamide trihydrochloride, a novel antagonist of serotonin receptor 5-HT2B (Ki = 5.2 nM, IC50 = 6.9 nM), when administered to rats for three weeks in daily oral 10 mg/kg doses, prevents not only monocrotaline (MCT)-induced elevations in pressure in the pulmonary arterial circuit (19 ± 0.9 mm Hg vs. 28 ± 2 mm Hg in MCT-vehicle group, P < 0.05) and hypertrophy of the right ventricle (right ventricular wt./body wt. ratio 0.52 ± 0.02 vs. 0.64 ± 0.04 in MCT-vehicle group, P < 0.05), but also muscularization of pulmonary arterioles (23% vs. 56% fully muscularized in MCT-vehicle group, P < 0.05), and perivascular fibrosis in the lung. C-122 is orally absorbed in the rat, and partitions strongly into multiple tissues, including heart and lung. C-122 has significant off-target antagonist activity for histamine H-1 and several dopamine receptors, but shows no evidence of crossing the blood–brain barrier after a single 10 mg/kg oral dose in rats. We conclude that C-122 can prevent microvascular remodeling and associated elevated pressures in the rat MCT model for PAH, and offers promise as a new therapeutic entity to suppress vascular smooth muscle cell proliferation in PAH patients. 相似文献
7.
Schlicker E. Göthert M. Hillenbrand K. 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(4):398-401
Summary Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution containing the serotonin uptake blocker DU 24565 (6-nitroquipazine). The effects of (±)-cyanopindolol and its enantiomers, of ICI 118,551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol) and of isoprenaline on the electrically (3 Hz) evoked 3H overflow were studied.(±)-Cyanopindolol increased the evoked 3H overflow; this effect was prevented by preexposure to the previously characterized serotonin receptor antagonist metitepin. The concentration-response curve of unlabelled serotonin for its inhibitory effect on the electrically evoked 3H overflow was shifted to the right by (±)-cyanopindolol (apparent pA2 value: 8.29), whereas that of noradrenaline (determined in the absence of DU 24565) was not affected (apparent pA2 value: <6.0). The concentration-response curve of serotonin was also shifted to the right by (–)-cyanopindolol (apparent pA2 value: 8.30) and (+)-cyanopindolol (6.83) but not by ICI 118,551 (<5.5). Isoprenaline (up to 10 mol/l; examined in the absence of DU 24565) did not influence the electrically evoked 3H overflow.The present results show that the presynaptic serotonin autoreceptor is blocked by cyanopindolol in a stereoselective way. This drug is 20 times more potent than metitepin as an antagonist at the presynaptic serotonin autoreceptor, and, in contrast to the latter, it does not act as an antagonist at the presynaptic 2-adrenoceptor on the serotoninergic neurone.This study was supported by a grant of the Deutsche Forschungsgemeinschaft 相似文献
8.
RATIONALE: The benzazepine and "selective" dopamine D1 receptor antagonist, SCH23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol], shows significant affinity at native serotonin (5-HT)2C receptors. OBJECTIVES: We examined its functional actions at cloned human (h)5-HT2C receptors (VSV isoform) stably expressed in CHO cells. METHODS: Since 5-HT2C receptors are positively coupled to phospholipase C (PLC), their activation was determined by depletion of membrane-bound pools of pre-labelled [3H]phosphotidylinositol ([3H]PI). RESULTS: SCH23390 showed high affinity (Ki, 9.3 nM) at h5-HT2C sites and depleted [3H]PI with an EC50 of 2.6 nM. Its efficacy was equivalent to that of 5-HT. [3H]PI depletion elicited by SCH23390 was concentration-dependently abolished by the selective 5-HT2C antagonist, SB242,084, with a K(B) of 0.55 nM. Further, in the presence of a fixed concentration of SB242,084 (10 nM), the concentration-response curve for SCH23390 was shifted to the right without loss of maximal effect, yielding a K(B) of 0.57 nM. CONCLUSIONS: SCH23390 is a potent and high efficacy agonist at h5-HT2C receptors. Activation of 5-HT2C receptors by SCH23390 may contribute to its functional properties both in animals and in humans. 相似文献