共查询到20条相似文献,搜索用时 15 毫秒
1.
Suleyman H Halici Z Cadirci E Hacimuftuoglu A Keles S Gocer F 《Naunyn-Schmiedeberg's archives of pharmacology》2007,375(3):189-198
Nimesulide, a non-steroidal, anti-inflammatory drug, produces ulcerogenic effects in adrenalectomized rats but is gastro-protective
in intact rats. The objective of this study was to determine whether adrenal gland hormones are involved in the anti-ulcer
effects of nimesulide. The results revealed that 100 mg/kg nimesulide produces gastric ulceration in adrenalectomized rats,
which is prevented by prednisolone and adrenaline. The anti-ulcer effects of adrenaline and prednisolone in adrenalectomized
rats were in turn antagonized by yohimbine, a selective α2-receptor blocker, but not by doxazosine (α1-receptor blocker) or propranolol (β-blocker). Adrenaline prevented the formation of indomethacin-induced ulcers in both adrenalectomized
and intact rats, but prednisolone increased the indomethacin-induced ulcerous area in intact rats, whereas it decreased the
size of the ulcers in adrenalectomized rats. In addition, prednisolone prevented ulcer formation in intact rats in which the
adrenaline concentration had been decreased by metyrosine. These results suggest that glucocorticoids are anti-ulcerogenic
in not only adrenalectomized rats but also in intact rats with diminished circulating levels of adrenaline. In the light of
these data, the effect of nimesulide on plasma adrenaline concentrations was studied. In comparison to the adrenaline levels
found in intact control rats, the administration of nimesulide at doses of 10, 20, 40 and 100 mg/kg decreased adrenaline concentrations
by 12.8, 22.6, 30.4, and 58.2%, respectively, without affecting blood corticosterone concentrations. The anti-ulcer effect
of nimesulide was observed to be dose-dependent, and the strength of this effect was directly correlated the decreasing concentration
of adrenaline. The concentration of adrenaline was decreased by 60.9% in rats treated with 300 mg/kg metyrosine in which prednisolone
produced anti-ulcer effects. In summary, we have shown that nimesulide produces its anti-ulcer effect by decreasing endogenous
adrenaline concentrations and that glucocorticoids may induce anti-ulcer effects via α2-adrenoreceptors, but not via their own receptors.
This research was conducted in the Laboratory of Pharmacology at Ataturk University, Faculty of Medicine, Department of Pharmacology,
25240 Erzurum/Turkey. 相似文献
2.
Mori A Nakahara T Sakamoto K Ishii K 《Naunyn-Schmiedeberg's archives of pharmacology》2011,384(6):603-608
The aim of this study was to determine the role of β3-adrenoceptors in the action of endogenous catecholamines (adrenaline and noradrenaline) on rat retinal arterioles in vivo.
Using an original high-resolution digital fundus camera, the rat ocular fundus images were captured. The diameter of retinal
arterioles contained in the images was measured. Both systemic blood pressure and heart rate were recorded continuously. Adrenaline
(0.3–5.0 μg/kg/min, i.v.) increased the diameter of retinal arterioles, mean blood pressure and heart rate in a dose-dependent
manner. Under blockade of β1/β2-adrenoceptors with propranolol (2 mg/kg, i.v. bolus followed by 100 μg/kg/min infusion), adrenaline decreased the diameter
of retinal arterioles. Similar observation was made under treatment with the β3-adrenoceptor antagonist L-748337 (50 μg/kg, i.v.). The pressor response to adrenaline was enhanced by propranolol, but not
by L-748337. The positive chronotropic action of adrenaline was markedly prevented by propranolol, whereas it was unaffected
by L-748337. Noradrenaline (0.03–1.0 μg/kg/min, i.v.) decreased the diameter of retinal arterioles but increased the mean
blood pressure and heart rate. The effects of noradrenaline on retinal arteriolar diameter and blood pressure were unaffected
by propranolol or L-748337. The positive chronotropic action of noradrenaline was almost completely abolished by propranolol.
These results suggest that β3-adrenoceptors play crucial roles in vasodilator responses to adrenaline of retinal arterioles but have minor or no effect
on noradrenaline-induced responses. The results also indicate that the functional role of β3-adrenoceptors may be more important than that in peripheral resistance vessels. 相似文献
3.
Plass H Charisius M Wyskovsky W Amor F Turnheim K Wiener H 《Naunyn-Schmiedeberg's archives of pharmacology》2005,371(6):492-499
To clarify the mechanism of the diarrhea associated with the clinical use of antiarrhythmic drugs we assessed the effects of these agents on transepithelial Na+ absorption and Cl- secretion, on basolateral K+ conductance, and on the properties of single basolateral K+ channels of rabbit colon epithelium. Quinidine and propafenone, both at 10 microM, inhibited Na+ absorption by 27 and 38% respectively, compared with 50% with 5 mM Ba2+. The other tested class I antiarrhythmics disopyramide, mexiletine, lidocaine, and flecainide decreased Na+ current by 9-13%. Procainamide and the class III antiarrhythmics N-acetylprocainamide, sotalol, ibutilide, and amiodarone were no or were very weak inhibitors of Na+ absorption. Cl- secretion, stimulated with the adenosine analogue NECA (5'-N-ethylcarboxamide-adenosine), was reduced by 54% with quinidine and by 29% with propafenone compared with 100% with Ba2+. Mexiletine, lidocaine, and flecainide inhibited Cl- secretion by 10-23%, whereas the class III antiarrhythmics were no or were weak inhibitors. Those antiarrhythmics that inhibited Na+ and Cl- transport also reduced basolateral K+ conductance, determined in amphotericin B permeabilized epithelia. The activity of the high-conductance, Ca2+-activated, voltage-dependent K+ (BK(Ca)) channel, which is primarily responsible for basolateral K+ recycling during Na+ absorption, was inhibited by 10-30 microM quinidine or propafenone in the form of a rapidly dissociating block. Mexiletine and flecainide inhibited the single channel conductance at higher concentrations; disopyramide, lidocaine, and procainamide were ineffective. In conclusion, the present evidence suggests that the diarrhea caused by class I antiarrhythmic drugs such as quinidine and propafenone is a result of a reduction in basolateral K+ conductance and inhibition of BK(Ca) channels, thereby impeding transepithelial Na+ and water absorption. 相似文献
4.
Nunn C Rueping M Langenegger D Schuepbach E Kimmerlin T Micuch P Hurth K Seebach D Hoyer D 《Naunyn-Schmiedeberg's archives of pharmacology》2003,367(2):95-103
Four linear beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptides (1-4) were investigated as somatostatin sst(4) receptor agonists on recombinant human and mouse somatostatin receptors. Human somatostatin receptor subtypes 1-5 (sst(1-5)), and mouse somatostatin receptor subtypes 1,3,4 and 5, were characterised using the agonist radioligands [(125)I]LTT-SRIF-28, [(125)I][Tyr(10)]CST(14) and [(125)I]CGP 23996 in stably transfected Chinese hamster lung fibroblast (CCL39) cells. The peptides bound selectively to sst(4) receptors with nanomolar affinity (pK(d)=5.4-7.8). The peptides were investigated on second messenger systems both as agonists, and as antagonists to SRIF-14-mediated effects in CCL39 cells expressing mouse sst(4 )receptors, via measurement of inhibition of forskolin-stimulated adenylate cyclase activity, and stimulation of luciferase expression. The peptides showed full agonism or pronounced partial agonism (40 to 100% relative intrinsic activity) in both inhibition of forskolin-stimulated adenylate cyclase activity (pEC(50)=5.5-6.8), and luciferase expression (pEC(50)=5.5-6.5). The agonist potential was confirmed since antagonism was very difficult to establish. The data show that beta(2)/beta(3)-di- and alpha/beta(3)-tetrapeptide derivatives have agonist potential at recombinant somatostatin sst(4) receptors. Therefore, they may be used to elucidate physiological and biochemical effects mediated by sst(4), and may also have potential as therapeutic agents. 相似文献
5.
Lin C Nagai M Ishigaki D Hayasaka K Endoh M Ishii K 《Naunyn-Schmiedeberg's archives of pharmacology》2005,371(2):133-140
Delayed rectifier K+ currents (IK) play a critical role in determining cardiac action potential duration (APD). Modulation of IK affects cardiac excitability critically. There are three components of cardiac delayed rectifier, and the slowly activating component (IKs) is influenced strongly by a variety of stimuli. Plasma levels of noradrenaline and endothelin are elevated in heart failure, and arrhythmias are promoted by such humoral abnormalities through modulation of ion channels. It has been reported that protein kinase A (PKA) and protein kinase C (PKC) modulate IKs from human minK in a complex manner. In the present study, we coexpressed human minK with the human 1-adrenoceptor (h1AR) and the endothelin receptor subtype A (hETAR) in Xenopus oocytes and investigated the effects of receptor activation on the currents (IKs) flowing through the oocytes. ET-1 modulated IKs biphasically: a transient increase followed by a decrease. The PKC inhibitor chelerythrine completely inhibited the effects of ET-1. Intracellular EGTA abolished the transient increase by ET-1 and partially inhibited the subsequent decrease in the currents. When IKs was increased by 10–6 M isoproterenol (ISO), ET-1 did not increase but rather decreased the current to an even greater extent than under control conditions. In addition, the effects of ISO on IKs were suppressed by ETAR stimulation. These data indicate that IKs can be regulated by cross-talk between the ETAR and 1AR systems in addition to direct regulation by each receptor system. 相似文献
6.
Mugisha P Gründemann D Schömig E Uhlén S 《Naunyn-Schmiedeberg's archives of pharmacology》2002,365(5):335-340
[(3)H]Prazosin bound to alpha(1A)- and alpha(1B)-adrenoceptors, as well as to a cimetidine-sensitive non-alpha(1)-adrenoceptor binding site in rat kidney membranes. An experimental design is presented where the alpha(1)-adrenoceptors are selectively exposed by blocking the non-alpha(1) binding site with 60 microM cimetidine. Conversely, the non-alpha(1) binding site can be selectively exposed by blocking the alpha(1)-adrenoceptors with 600 nM metitepine. The identity of the non-alpha(1) binding site for [(3)H]prazosin in the rat kidney, herein pharmacologically characterized by 33 competing substances, is still unknown. 相似文献
7.
Carman-Krzan M Bavec A Zorko M Schunack W 《Naunyn-Schmiedeberg's archives of pharmacology》2003,367(5):538-546
We determined the molecular properties of the selective and potent H(1)-receptor agonist histaprodifen and its N(alpha) substituted analogues: methyl-, dimethyl-, and imidazolylethyl-histaprodifen (suprahistaprodifen). All derivatives show high affinity for (3)H-mepyramine labeled bovine aortic H(1)-receptor binding sites with the following order of potency: suprahistaprodifen > dimethylhistaprodifen > methylhistaprodifen > histaprodifen > histamine. Suprahistaprodifen and dimethylhistaprodifen were the most potent displacers of (3)H-mepyramine binding (K(i)=4.3 and 4.9 nM, respectively). Histaprodifen, methylhistaprodifen and suprahistaprodifen binding was differentially influenced by GTP, whereas dimethylhistaprodifen was not affected. All drugs, except dimethylhistaprodifen, were activators of G-proteins. Their order of potency was suprahistaprodifen > histamine > histaprodifen > methylhistaprodifen. Their effect on G-protein activation was abolished by the addition of the H(1)-receptor antagonist triprolidine (10 microM), which given alone did not activate G-proteins. Our data suggest that histaprodifens are potent but heterogeneous H(1)-receptor ligands with diverse effects on the molecular level in our model system. While the histaprodifen, methylhistaprodifen and suprahistaprodifen data are in agreement with their agonistic nature, as shown in the functional studies performed on different species (rat and guinea pig H(1)-receptor), dimethylhistaprodifen behaved as an antagonist in our study. 相似文献
8.
Egashira N Manome N Mishima K Iwasaki K Oishi R Fujiwara M 《Psychopharmacology》2012,219(4):1111-1118
Rationale
Cannabis is a widely used illicit substance. ∆9-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive deficits that closely resemble the impairment observed in schizophrenic patients. We previously reported that THC (6 mg/kg) impairs spatial memory in the eight-arm radial maze, and that this memory disturbance was reversed by the cannabinoid CB1 receptor antagonist rimonabant (0.1 mg/kg), suggesting that the effect of THC is mediated through cannabinoid CB1 receptors. 相似文献9.
Abstract
Rationale. Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) or WIN-55,212–2 (WIN-2) have psychoactive effects on cognition. As a result, the reinforcing properties of Δ9-THC or WIN-2 may confound learning and memory tests with false negative results. It therefore seems advisable to assess the
reinforcing properties of the drugs in the same behavioural model used for learning experiments.
Objective. We therefore developed conditioned place preference protocols in the open-field water maze and tested both Δ9-THC (2 mg/kg) and WIN-2 (1 mg/kg and 3 mg/kg). Given that previous reports on cannabinoids have revealed conflicting data
and that this was a novel behavioural test, we also tested the benzodiazepine receptor agonist diazepam (2.5 mg/kg). Some
methodical refinements were appropriate in order to determine the behavioural strategy implemented by the animals.
Methods. All animals were injected intraperitoneally 30 min prior to training/testing. In experiment 1, male hooded Lister rats injected
with drug were repeatedly placed on the drug-related platform and subsequently tested for place preference. In experiment
2, rats were trained to swim to the drug platform on drug days and to the vehicle platform on vehicle days. A series of probe
trials was introduced to delineate what had been learned. Experiment 3 studied the effect of WIN-2 on spatial learning in
the water maze.
Results. Neither WIN-2 nor Δ9-THC induced place preference in the water maze. When trained in the swim procedure, however, WIN-2 was neutral, but Δ9-THC resulted in place aversion. Conversely, diazepam consistently produced place preference in both procedures. WIN-2 (3 mg/kg),
however, produced a small learning deficit in the spatial water maze task.
Conclusion. It appears that the reinforcing properties of Δ9-THC and WIN-2 in the doses used here are different, despite them both being agonists at cannabinoid receptors within the
central nervous system. The fact that Δ9-THC may be aversively related to a particular context has implications for previous work reporting deficits in spatial learning.
Electronic Publication 相似文献
10.
Qiang Wei Li Liu Zhe Cong Xiaoxian Wu Hui Wang Chuan Qin Patricia Molina Zhiwei Chen 《Journal of neuroimmune pharmacology》2016,11(3):584-591
Delta9-tetrahydrocannabinol (Δ9-THC) is the major psychoactive component of the cannabis plant. Δ9-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ9-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ9-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ9-THC+SIV+, Δ9-THC+SIV?, PBO/SIV+ and PBO/SIV? (n = 4/group). One-month after daily Δ9-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ9-THC+SIV+ and PBO/SIV+ macaques. Regardless of Δ9-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4+ T cells and higher persistent levels of Ki67+CD8+ T cells compared with uninfected animals. Moreover, long-term Δ9-THC treatment reduced significantly the frequency of circulating IgE+B cells. Only one Δ9-THC+SIV+ macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV+ group during the study period. These findings indicate that chronic Δ9-THC administration resulted in reduction of IgE+B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin. 相似文献
11.
The ability of the human 5-HT1A receptor to activate different recombinant G proteins was investigated in CHO-K1 cells by monitoring 5-HT ligand-mediated Ca2+ responses upon co-expression with either Gq, G15 or chimeric Gq/i3 proteins. Each G protein yielded a typical 5-HT-dependent Ca2+ response with different kinetic parameters both for the onset-time of maximal Ca2+ response (21 to 30 s) and time-dependent attenuation (43 to 73% of residual activity at 1 min upon peak Ca2+ response). Pertussis toxin-treatment fully abolished the Ca2+ responses mediated by both the endogenous Gi/o and the chimeric-PTX-sensitive Gq/i3 proteins. In contrast, Ca2+ responses driven by recombinant Gq and G15 proteins were decreased by PTX, respectively by 52% and 35%, corresponding to the level of endogenous G protein activation. The pharmacology of the 5-HT ligand-mediated Ca2+ responses was highly affected by both the presence and nature of the co-expressed G protein. This influence was more pronounced for the partial agonists L 694247, 8-OH-DPAT, flesinoxan and buspirone in contrast to ipsapirone. The G protein rank order for apparent increase of ligands' intrinsic activity was: Gq <Gq/i3 <G15 protein. Each of the 5-HT-mediated Ca2+ responses could be antagonised by WAY 100635, buspirone and methiothepin regardless of the absence or presence of a Gq, Gq/i3 or G15 protein. In conclusion, these data reinforce that depending on the presence and nature of the G protein environment, 5-HT1A ligands may display a large spectrum of activities.Abbreviations AFU Arbitrary fluorescence unit - 5-CT 5-Carboxamidotryptamine - 5-HT 5-Hydroxytryptamine (serotonin) - 8-OH-DPAT 8-(Hydroxy-2-(di-n-propylamino)tetralin - CHO Chinese hamster ovary - PLC Phospholipase C - WAY 100635 N-[2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide - PTX Bordetella pertussis toxin - wt Wild-type 相似文献
12.
The 2-adrenoreceptor antagonist idazoxan counteracts catalepsy induced by neuroleptic agents and improves Parkinsonian signs in 1-methyl-4-phenyl 1,2,3,6,tetrahydropyridine-treated monkeys and in patients. The present study addressed the question of whether systemic administration of idazoxan (1.5 mg/kg i.p.) improves Parkinsonian symptoms in a rat model of permanent dopaminergic neurodegeneration. Dopaminergic degeneration was induced by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). Parkinsonian behaviour was assessed by catalepsy and open-field exploratory behaviour tests. Since dopaminergic and serotonergic mechanisms are thought to account for the anti-cataleptic/anti-Parkinsonian property of idazoxan, dopamine, 5-hydroxytryptamine (5-HT) and its metabolites in the regions of the basal ganglia and prefrontal cortex were analysed by HPLC. 6-OHDA lesions in the MFB produced catalepsy and hypoactivity in the open field and depleted dopamine and its metabolites in the basal ganglia and prefrontal cortex, but did not affect 5-HT. Treatment with idazoxan counteracted the observed Parkinsonian behaviour in 6-OHDA-lesioned rats and increased the spontaneous open-field activity in control rats. In both 6-OHDA and control animals, idazoxan increased DA level in the prefrontal cortex, but not in any other structures including the striatum. Idazoxan also increased the levels of 5-HT in the anterior striatum, prefrontal cortex and the ventral tegmental area of both 6-OHDA and control animals. These findings indicate that systemic administration of idazoxan counteracts 6-OHDA-induced Parkinsonian symptoms in rats and that both dopaminergic and serotonergic mechanisms could contribute to its anti-Parkinsonian effect. 相似文献
13.
Van Kampen M Selbach K Schneider R Schiegel E Boess F Schreiber R 《Psychopharmacology》2004,172(4):375-383
Rationale Nicotine and agonists at 42 and 7 nicotinic acetylcholine receptors (nAChRs) improve learning and memory. The 7-nAChR subtype is of special interest, since it appears to play no role in the abuse liability of nicotine.Objectives and methods To further investigate the role of the 7-nAChR in learning and memory, the effects of the specific 7-nAChR agonist AR-R17779 on cognition were measured in the rat social recognition test (SRT) and the effect of the 7-nAChR antagonist methyllycaconitine (MLA) was studied. The SRT and a scopolamine-induced deficit version were validated with the acetylcholinesterase inhibitor metrifonate. Social memory was measured by the ability of an adult rat to recognize a juvenile rat after a delay. The difference in social interaction time (SIT) was measured between two encounters. The difference in SIT is expressed as percent reduction in social interaction time (%RSIT).Results Metrifonate (10 and 30 mg/kg PO) increased %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR-R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and 1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg SC) in unimpaired animals were reversed by MLA (10 µg ICV), which induced a decrease of %RSI at a 15-min retention interval when given alone.Conclusions AR-R17779 increased social recognition memory by activation of 7-nAChRs, suggesting that 7-nAChR agonists possess cognitive-enhancing properties. 相似文献
14.
15.
Joseph SS Lynham JA Colledge WH Kaumann AJ 《Naunyn-Schmiedeberg's archives of pharmacology》2004,369(5):525-532
To verify the hypothesis that the non-conventional partial agonist (–)-CGP12177 binds at two 1-adrenoceptor sites, human 1-adrenoceptors, expressed in CHO cells, were labelled with (–)-[3H]-CGP12177. We compared the binding affinity and antagonist potency of 12 clinically used -blockers against the cyclic AMP-enhancing effects of (–)-isoprenaline and (–)-CGP12177.(–)-[3H]-CGP12177 bound to a high affinity site (H; KH=0.47 nM) and low affinity site (L); KL=235 nM). (–)-[3H]-CGP12177 dissociated from the 1-adrenoceptors with a fast component (koff=0.45 min–1), consistent with the L-site, and a slow component (koff=0.017–0.033 min–1), consistent with the H-site. (–)-Isoprenaline and (–)-CGP12177 caused 96-fold and 12-fold maximal increases in cyclic AMP levels with –logEC50M of 8.2 and 7.6. (–)-CGP12177 antagonised the effects of (–)-isoprenaline with a pKB of 9.9. The -blockers antagonised the effects of (–)-isoprenaline more than the effects of (–)-CGP12177 with potency ratios: (–)-atenolol 1,000, (±)-metropolol 676, (–)-pindolol 631, (–)-timolol 589, (±)-carvedilol 204, (±)-oxprenolol 138, (±)-sotalol 132, (–)-propranolol 120, (±)-bisoprolol 95, (±)-alprenolol 81, (±)-nadolol 68 and (–)-bupranolol 56. In intact cells the binding constants of -blockers, estimated from competition with 3–5 nM (–)-[3H]-CGP12177 (binding to the H-site), correlated with the corresponding affinities estimated from antagonism of the (–)-isoprenaline effects.We conclude that (–)-[3H]-CGP12177 binds at two sites in the recombinant 1-adrenoceptor. (–)-CGP12177 is an antagonist of catecholamine effects through the H-site and a non-conventional partial agonist through the L-site. -blockers are more potent antagonists through the H-site than the L-site. 相似文献
16.
The Spontaneously Hypertensive rat (SHR) has been previously shown to have a host of neurochemical differences compared with their normotensive counterpart, the Wistar–Kyoto (WKY) rat. Using quantitative receptor autoradiography, the density of GABAA and NMDA receptors and [3H]cGMP binding within the locus coeruleus (LC) and central pontine grey (CGPn) were compared in the SHR and WKY rat using the radioligands [3H]SR95531, [3H]MK-801 and [3H]cGMP respectively. It was found that [3H]SR95531 binding was significantly greater in both the LC and CGPn of the SHR compared with the WKY rat (unpaired t test; P<0.05). Greater binding densities of [3H]MK-801 and [3H]cGMP were also observed in the LC of the SHR compared with the WKY rat; however, no differences in the binding density of these two ligands were observed in the CGPn. It is suggested that these neurochemical differences within the LC of the SHR may relate to phenotypic differences between SHR and WKY rats that have previously been reported. 相似文献
17.
Rebouças EC Segato EN Kishi R Freitas RL Savoldi M Morato S Coimbra NC 《Psychopharmacology》2005,179(2):349-355
Rationale Sweet-substance-induced analgesia has been widely studied, and the investigation of the neurotransmitters involved in this antinociceptive process is an important way for understanding the involvement of the neural system controlling this kind of antinociception.Objective The aim of this study was to investigate the involvement of opioid and monoaminergic systems in sweet-substance-induced analgesia.Methods The present work was carried out in an animal model with the aim of investigating whether acute (24 h) or chronic (14 days) intake of a sweet substance, such as sucrose (250 g/l), is followed by antinociception. Tail withdrawal latencies in the tail-flick test were measured before and immediately after this treatment. Immediately after the recording of baseline values, independent groups of rats were submitted to sucrose or tap-water intake and, after chronic treatment, they were pretreated with intraperitoneal administration of (1) naltrexone at 0.5, 1, 2 or 3 mg/kg; (2) naloxonazine at 5, 10, 20 or 30 mg/kg; (3) methysergide at 0.5, 1, 2 or 3 mg/kg; (4) ketanserin at 0.5, 1, 2 or 3 mg/kg; or (5) physiological saline.Results Naltrexone and methysergide at two major doses decreased sweet-substance-induced analgesia after chronic intake of a sweet substance. These effects were corroborated by peripheral administration of naloxonazine and ketanserin.Conclusions These data give further evidence for: (a) the involvement of endogenous opioids and a 1-opioid receptor in the sweet-substance-induced antinociception; (b) the involvement of monoamines and 5HT2A serotonergic/1-noradrenergic receptors in the central regulation of the sweet-substance-produced analgesia. 相似文献
18.
Abstract
Rationale. The discriminative stimulus effects of zolpidem in squirrel monkeys trained at doses greater than or equal to 3.0 mg/kg differ
from those of conventional benzodiazepines (BZs), but the extent to which these effects reflect the selectivity of zolpidem
for GABAA/α1 receptors is not known.
Objectives. The present study investigated the ability of GABAA/α1-preferring agonists to substitute for training doses of zolpidem greater than or equal to 3.0 mg/kg and the ability of GABAA/α1-preferring antagonists to block zolpidem's discriminative stimulus effects.
Methods. Squirrel monkeys were trained to discriminate intravenous injections of zolpidem (3.0 or 5.6 mg/kg) from saline and tested
with BZ agonists differing in selectivity and efficacy at GABAA/α1 receptors. Antagonism of the effects of zolpidem was studied using the GABAA/α1-preferring antagonists β-carboline-3-carboxylate-t-butyl ester (β-CCT) and 3-propyloxy-β-carboline (3-PBC).
Results. Zolpidem and quazepam (GABAA/α1-preferring agonist) engendered full substitution for zolpidem, whereas CL 218,872 (GABAA/α1-preferring partial agonist) and the non-selective BZ agonists alprazolam and flunitrazepam engendered low and variable levels
of zolpidem-lever responding (35–58%). Both β-CCT and 3-PBC antagonized the discriminative stimulus effects of zolpidem in
a surmountable fashion.
Conclusions. Our findings provide evidence for a key role of GABAA/α1 receptors in the discriminative stimulus effects of zolpidem at relatively high training doses, and suggest that selectivity
and relatively high efficacy at GABAA/α1 receptors is required for BZ agonists to reproduce these discriminative stimulus effects.
Electronic Publication 相似文献
19.
Rationale Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component 9-tetrahydrocannabinol (9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats.Methods To determine the effects of pretreatment with 9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of 9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of 9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of 9-THC or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with 9-THC (0.25–1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle.Results 9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own.Conclusions These results are the first to show that both 9-THC, which acts on both CB1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning. 相似文献
20.
Myslivecek J Rícný J Kolár F Tucek S 《Naunyn-Schmiedeberg's archives of pharmacology》2003,368(5):366-376
Glucocorticoids affect the expression and density of neurotransmitter receptors in many tissues but data concerning the heart are contradictory and incomplete. We injected rats with hydrocortisone for 1–12 days and measured the densities of cardiac muscarinic receptors, 1-, 1- and 2-adrenoceptors and propranolol-resistant binding sites (formerly assumed to be the putative 4-adrenoceptor). Some aspects of intracellular signalling were also evaluated: we measured adenylyl cyclase activity (basal, isoprenaline- and forskolin-stimulated and carbachol-inhibited), the coupling between muscarinic receptors and G proteins and basal and isoprenaline-stimulated heart rate. The density of cardiac muscarinic receptors increased (in both the atria and the ventricles). The density of 1-adrenoceptors increased in the atria and was little changed in the ventricles. The density of 2-adrenoceptors increased in both the atria and the ventricles. The number of 1-adrenoceptors decreased initially, followed by a transient increase in the atria and did not change in the ventricles. The density of propranolol-resistant binding sites first increased and then diminished in the atria and did not change in the ventricles. Although there were noticeable changes in receptor densities, the stimulatory and inhibitory effects on adenylyl cyclase, basal and isoprenaline-stimulated heart rate and the coupling between muscarinic receptors and G proteins were not significantly altered. This may indicate that changes in receptor densities might be one of the mechanisms maintaining stable functional output. Deceased 相似文献