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1.
The effect of the non-selective 5-HT2C receptor agonist trifluoromethyl-phenylpiperazine (TFMPP, 0.75, 1.5 and 3.0 microg) and the preferential 5-HT2C agonist 6-chloro-2(1-piperazinyl)pyrazine (MK-212, 0.1, 0.3 and 1.0 microg) microinjected into the ventral or dorsal hippocampus was investigated in anxiety measures of rats exposed to the elevated plus-maze test. Ventral hippocampal (VH) microinjections of the 0.75 or 1.5 microg doses of TFMPP reduced open-arm exploration without affecting the number of closed-arm entries, indicating a selective anxiogenic profile. The highest dose (3.0 microg) reduced open- and closed-arm entries, suggesting interference in locomotor activity. The 0.1 microg dose of MK-212 also caused a selective anxiogenic effect when microinjected into the ventral hippocampus, without disturbing locomotor activity. Microinjections of the two higher doses of MK-212 (0.3 or 1.0 microg) into the ventral hippocampus led to a decrease of exploration in both arms of the maze. In contrast to the anxiogenic effect observed in the VH, neither TFMPP nor MK-212 significantly changed anxiety measures when microinjected into the dorsal hippocampus. These results suggest that activation of 5-HT2C postsynaptic receptors located in the ventral, but not in the dorsal, hippocampus play an important role in anxiety triggered by the elevated plus-maze test. 相似文献
2.
The cardiovascular effects of quipazine are mediated by peripheral 5-HT2 and 5-HT3 receptors in anaesthetized rats 总被引:2,自引:0,他引:2
C Vayssettes-Courchay F Bouysset T J Verbeuren M Laubie H Schmitt 《European journal of pharmacology》1990,184(1):75-85
Quipazine (0.5-2 mg/kg i.v.) produced transient hypotension and bradycardia followed by sustained hypertension and variable effects on heart rate in anaesthetized rats. The hypotension, bradycardia and sympatho-inhibitory effects of quipazine were attenuated by bivagotomy. In bivagotomized rats, the hypertension produced by quipazine was not modified by hexamethonium or prazosin but was abolished by ritanserin (1 mg/kg i.v.). In ritanserin-treated rats, section of the carotid sinus nerves and vagus nerves or ICS 205.930 (0.1 mg/kg i.v.) abolished the hypotensive, bradycardic and sympatho-inhibitory effects of quipazine; the action of quipazine was not reproducible in these rats. Quipazine also inhibited the Bezold-Jarish reflex elicited by 5-HT (20 micrograms/kg i.v.). In ICS 205.930-treated rats, the hypertension evoked by quipazine was associated with a reduction in splanchnic nerve activity due to stimulation of baroreceptors. The renin-angiotensin system is not involved in the hypertensive response. The increase in heart rate produced by quipazine in bivagotomized rats was reduced by ritanserin and tertatolol (0.1 mg/kg i.v.) and abolished by a combination of both drugs. We conclude that the bradycardic and sympatho-inhibitory effects of quipazine result from activation of 5-HT3 receptors located in the cardiopulmonary area and of carotid body chemoreceptors. The hypertension and tachycardia are mediated by vascular and myocardial 5-HT2 receptors. No evidence was obtained for a central sympatho-excitatory effect. 相似文献
3.
BACKGROUND AND PURPOSE: The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5-HT receptors (5-HT1-7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5-HT7 receptor. We aimed to examine the role of spinal 5-HT7 receptors in the antinociceptive effects of systemic morphine. EXPERIMENTAL APPROACH: The involvement of spinal 5-HT7 receptor in systemic morphine antinociception was compared to that of the 5-HT1A and 5-HT2 receptors by using the selective 5-HT7 receptor antagonist, SB-269970, the selective 5-HT1A receptor antagonist, WAY 100635, the selective 5-HT2 antagonist ketanserin as well as the non-selective 5-HT1,2,7 receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail-flick test. KEY RESULTS: I.t. administration of SB-269970 (10 microg) and metergoline (20 microg) completely blocked the s.c. administered morphine-induced (1, 3, 5 and 10 mg kg(-1)) antinociception in a time-dependent manner. Additionally, i.t. administration of SB-269970 (1, 3, 10 and 20 microg) and metergoline (1, 5, 10 and 20 microg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10 mg kg(-1), s.c.). I.t. administration of WAY 100635 (20 microg) or ketanserine (20 microg) did not alter morphine-induced (1, 3, 5 and 10 mg kg(-1), s.c.) antinociception. CONCLUSION AND IMPLICATIONS: These findings indicate that the involvement of spinal 5-HT7, but not of 5-HT1A or of 5-HT2 receptors in the antinociceptive effects of systemic morphine. 相似文献
4.
5-HT1A receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5-HT neurons in the median raphe nucleus. 总被引:1,自引:0,他引:1
Lucinéia Dos Santos Telma G C S de Andrade Hélio Zangrossi Junior 《European neuropsychopharmacology》2008,18(4):286-294
We evaluated the involvement of dorsal hippocampus (DH) 5-HT1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-maze test of anxiety. The results showed that intra-DH injection of the 5-HT1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT1A antagonist WAY-100635 was ineffective. In the elevated T-maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory amino acid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre-administration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN. 相似文献
5.
Rationale
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects in rodents and humans after systemic administration. Previous results from our group showed that CBD injection into the bed nucleus of the stria terminalis (BNST) attenuates conditioned aversive responses. The aim of this study was to further investigate the role of this region on the anxiolytic effects of the CBD. Moreover, considering that CBD can activate 5-HT1A receptors, we also verified a possible involvement of these receptors in those effects.Methods
Male Wistar rats received injections of CBD (15, 30, or 60?nmol) into the BNST and were exposed to the elevated plus-maze (EPM) or to the Vogel conflict test (VCT), two widely used animal models of anxiety.Results
CBD increased open arms exploration in the EPM as well as the number of punished licks in the VCT, suggesting an anxiolytic-like effect. The drug did not change the number of entries into the enclosed arms of the EPM nor interfered with water consumption or nociceptive threshold, discarding potential confounding factors in the two tests. Moreover, pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.37?nmol) blocked the effects of CBD in both models.Conclusions
These results give further support to the proposal that BNST is involved in the anxiolytic-like effects of CBD observed after systemic administration, probably by facilitating local 5-HT1A receptor-mediated neurotransmission. 相似文献6.
C Polidori P L Pompei M Perfumi C Melchiorre M Massi 《European journal of pharmacology》1991,195(1):139-143
The present study investigated the effect of selective muscarinic antagonists on natriuresis, kaliuresis and antidiuresis induced by intracerebroventricular (i.c.v.) injection of carbachol in the rat. The muscarinic antagonists were given by i.c.v. injection 1 min before carbachol (1 microgram/rat). 4-Diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a rather selective M1 and M3 receptor antagonist, was the most potent inhibitor of carbachol-induced natriuresis, kaliuresis and antidiuresis, its ID50 being respectively 0.12, 0.04 and 0.56 nmol/rat. Pirenzepine, a selective M1 antagonist, potently inhibited the above mentioned carbachol effects, its ID50 being 1.85, 3.25 and 1.49 nmol/rat, respectively. On the other hand, the M2-selective antagonist methoctramine and the M3-selective antagonist p-fluoro-hexahydro-sila-difenidol were very weak inhibitors. Methoctramine at doses up to 60 nmol/rat produced non statistically significant inhibition of carbachol-induced natriuresis, kaliuresis and antidiuresis. Para-fluoro-hexahydro-sila-diphenidol showed an ID50 of 64.4 nmol/rat on carbachol-induced natriuresis, while at the maximum dose employed, 100 nmol/rat, the inhibition of carbachol-induced kaliuresis and antidiuresis was lower than 50%. The rank order of potency of the antagonists tested proved to be related to their pA2 values for muscarinic M1 receptors, suggesting that this receptor subtype mediates the central effects of cholinergic mechanisms on water and electrolyte excretion. 相似文献
7.
Rodrigo Andrade 《Drug development research》1992,26(3):275-286
Electrophysiological recordings from hippocampus and cortex have demonstrated that one of the most prominent effects of serotonin in these regions is a membrane hyperpolarization that effectively inhibits neuronal activity. The use of the in vitro brain slice preparation has allowed for detailed pharmacological and physiological studies of this response. Pharmacological analysis using agonists and antagonists indicates that these responses are mediated by activation of receptors of the 5-HT1A subtype. Buspirone, ipsapirone and 8-OHDPAT are all partial agonists at this receptor with 8-OHDPAT exhibiting an intrinsic activity approximately one-fourth that of serotonin. The ability of 5-HT1A receptor agonists to elicit a hyperpolarization is dependent on intracellular GTP, suggesting the involvement of a G protein in the transmembrane signalling mechanism. In agreement with this idea, injection of the stable GTP analog GTPγS renders the serotonin induced hyperpolarization irreversible, while GDPβS blunts its effects and pertussis toxin pretreatment blocks it. The 5-HT1A receptor induced hyperpolarization is mediated by an increase in potassium conductance. While the identity of the potassium channel remains to be determined, its basic characteristics identify it as belonging to a general class of inwardly rectifying G protein activated potassium channels ubiquitously distributed in neuronal and cardiac muscle tissues. In the rat hippocampus and cortex, most pyramidal cells co-express 5-HT1A with either 5-HT4 or 5-HT2 receptors, respectively, which in turn act to increase the ability of strong stimuli to excite these cells. As a result the net effect of serotonin on membrane excitability is dependent on the strength of incoming stimuli. Weak stimuli are depressed by the coactivation of these receptor subtypes while strong stimuli are enhanced. Thus the effects of selective 5-HT1A ligands are likely to depend not only on their direct effect on membrane excitability but also on how they alter ongoing serotonergic neurotransmission. © 1992 Wiley-Liss, Inc. 相似文献
8.
The present study determined the mechanism by which yohimbine inhibits sympathetic nerve activity in the anesthetized cat. Low i.v. doses of yohimbine increased inferior cardiac nerve discharge as a result of the alpha 2-adrenoceptor antagonist properties of the drug. Higher doses of yohimbine (0.8-1.6 mg/kg) inhibited sympathetic nerve discharge. The inhibition of nerve activity was reversed by i.v. administration of the 5HT1A receptor antagonist spiperone. Similarly we have previously observed spiperone reversal of the sympatholytic effects of the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) but failed to affect nerve activity when given alone. Spiperone failed to reverse the sympatholytic effect of clonidine. These data indicate that high doses of yohimbine inhibit sympathetic nerve activity via a 5HT1A agonist action. 相似文献
9.
Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors. 总被引:6,自引:5,他引:1
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A. H. Bom J. P. Heiligers P. R. Saxena P. D. Verdouw 《British journal of pharmacology》1989,97(2):383-390
1. The potent, antimigraine drug ergotamine has affinity for both 5-HT1 and 5-HT2 binding sites and constricts arteriovenous anastomoses. Since 5-HT also constricts arteriovenous anastomoses (mainly via 5-HT1-like receptors), this study investigates the involvement of 5-HT receptors in the ergotamine-induced reduction of arteriovenous shunting in the carotid circulation of the cat and pig. 2. In the cat, ergotamine (3, 10 and 30 micrograms kg-1, i.v.) reduced carotid blood flow, predominantly by a reduction in arteriovenous anastomotic blood flow. Pretreatment with ketanserin (0.5 mg kg-1, i.v.) or methiothepin (1 mg kg-1, i.v.) did not antagonize the effects of ergotamine. 3. In the pig, ergotamine (2.5, 5, 10 and 20 micrograms kg-1, i.v.) also reduced carotid blood flow and arteriovenous shunting, which was not affected by pretreatment with methiothepin (1 mg kg-1, i.v.). 4. These results suggest that the reduction by ergotamine in the shunting of carotid arterial blood via cephalic arteriovenous anastomoses is not mediated by 5-HT1-like or 5-HT2 receptors. 相似文献
10.
Stimulation of 5-HT1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats. 总被引:1,自引:0,他引:1
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1. We studied whether the stimulation of 5-HT1A receptors by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a specific 5-HT1A receptor agonist, reduced electroencephalographic (EEG) seizures induced by intrahippocampal injection of 0.04 microgram in 0.5 microliter of the glutamate analogue kainic acid in freely-moving rats. 2. Pretreatment with 8-OH-DPAT 15 min earlier at the same site as kainic acid injection, caused a dose-dependent decrease of kainic acid-induced seizure activity. One and 10 micrograms significantly reduced the total time spent in seizures by 72% on average and the total number of seizures by 58% (P < 0.01) and 43% (P < 0.05) respectively. The latency to onset of the first seizure was increased 2.8 times (P < 0.01) only after 1 microgram 8-OH-DPAT; 0.1 microgram was ineffective on all seizure parameters. 3. Systemic administration of 25, 100 and 1000 micrograms kg-1 8-OH-DPAT significantly reduced the total number of seizures and the total time in seizures induced by intrahippocampal kainic acid by 52% and 74% on average. The latency to onset of the first seizure was delayed 1.8 times by 100 and 1000 micrograms kg-1 (P < 0.05). 4. The anticonvulsant action of 8-OH-DPAT given intrahippocampally or systemically was significantly blocked by 5 micrograms, but not 1 microgram WAY 100635, a selective 5-HT1A receptor antagonist, administered in the hippocampus before the agonist. 5. These results indicate that postsynaptic 5-HT1A receptors in the hippocampus mediate the anticonvulsant action of 8-OH-DPAT and that their stimulation has an inhibitory role in the generation of limbic seizures. 相似文献
11.
Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion 总被引:1,自引:0,他引:1
8-OH-DPAT, a selective 5-HT1A agonist, and mCPP, which has preferential affinity for 5-HT1B and 5-HT1C receptors, were studied for their effects on aversive brain stimulation in rats. Opposite effects were found with these two agonists: D, L-8-hydroxy-N,N-dipropyl-2-aminotetralin HBr (8-OH-DPAT; 0.1-1.0 mg/kg i.p.) dose dependently decreased the threshold for neurostimulation-induced escape behaviour while mCPP (0.1-1.0 mg/kg i.p.) dose dependently increased the threshold. The proaversive effect of 8-OH-DPAT and the antiaversive effect of mCPP suggest that 5-HT1A and non-5-HT1a (5-HT1B or 5-HT1C) receptors play distinct roles in mechanisms of aversion, perhaps at different locations in the CNS. 相似文献
12.
Hans O. Kalkman 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(5):583-584
The locomotor response to RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl) 1H-indole; 10 mg/kg, s.c.), a preferential 5-HT1B receptor agonist, was investigated in the rat, using two novel 5-HT1A receptor antagonists, WAY-100635 (0.3 mg/kg and 1 mg/kg, s.c.) and SDZ 216-525 (0.3 mg/kg, s.c.), and the novel 5-HT1B/5-HT1D receptor antagonist, GR 127935 (1 mg/kg, s.c.). The antagonists per se did not alter spontaneous locomotion. Both selective 5-HT1A receptor antagonists blocked RU 24969-induced hyperlocomotion, whilst the 5-HT1B receptor antagonist was without effect. These results suggest that RU 24969-induced hyperlocomotion in the rat is mediated by 5-HT1A receptors. 相似文献
13.
In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors. 相似文献
14.
Li X Inoue T Abekawa T Weng S Nakagawa S Izumi T Koyama T 《European journal of pharmacology》2006,532(1-2):74-80
Evidence from preclinical and clinical studies has shown that 5-HT(1A) receptor agonists have anxiolytic actions. The anxiolytic actions of 5-HT(1A) receptor agonists have been tested by our previous studies using fear conditioning. However, little is known about the brain regions of anxiolytic actions of 5-HT(1A) receptor agonists in this paradigm. In the present study, we investigated the effects of bilateral microinjections of flesinoxan, a selective 5-HT(1A) receptor agonist, into the hippocampus, amygdala and medial prefrontal cortex on the expression of contextual conditioned freezing and the defecation induced by conditioned fear stress in rats. These results reveal that both intrahippocampal and intraamygdala injections of flesinoxan decreased the expression of conditioned freezing, while injections into the medial prefrontal cortex did not. In addition, intraamygdala injection of flesinoxan attenuated the increased defecation induced by conditioned fear, but injections into the hippocampus and medial prefrontal cortex failed. These results suggest that flesinoxan exerts its anxiolytic actions in the fear conditioning through stimulations of the postsynaptic 5-HT(1A) receptors in the hippocampus and amygdala. 相似文献
15.
8-OH-DPAT [8-hydroxy-2-(di-N-propylamino)tetralin], a 5-HT(1A) receptor agonist, and S 15535 (4-benzodioxan-5-yl)1-(indan-2-yl)piperazine, a partial agonist at 5-HT(1A) receptors, were administered into the dorsal raphe nucleus and dorsal hippocampus and their behavioral effects were assessed in a modified Geller-Seifter conflict model. Injected into the dorsal raphe nucleus 8-OH-DPAT, 1 microg but not 0.04 or 0.2 microg 0.5 microl(-1), and S 15535, 2.5 microg but not 0.1 or 0.5 microg 0.5 microl(-1), significantly increased punished responding with no effect on rates of unpunished or time-out responding. WAY 100635, a selective 5-HT(1A) receptor antagonist, injected subcutaneously at 0. 3 mg kg(-1) 30 min before 1 microg 8-OH-DPAT or 2.5 microg S 15535 in the dorsal raphe, completely antagonized their effects on punished responding. At doses ranging from 1 to 10 microg microl(-1) injected into the CA1 region of the dorsal hippocampus neither 8-OH-DPAT nor S 15535 modified punished responding or the rates of time-out. At the highest doses, 8-OH-DPAT significantly reduced unpunished responding whereas S 15535 had the opposite effect. The results suggest that stimulation of 5-HT(1A) receptors in the dorsal raphe nucleus has anxiolytic-like effects whereas stimulation of postsynaptic receptors in the dorsal hippocampus has no anxiolytic or anxiogenic effects, at least judging from changes in rates of punished responding. These results are compatible with the hypothesis that 5-HT(1A) receptor agonists and partial agonists attenuate anxiety by reducing serotonergic transmission in brain areas innervated by the dorsal raphe nucleus. 相似文献
16.
Nicotine has bimodal effects on anxiety, with low doses having an anxiolytic effect and high doses having an anxiogenic effect. The dorsal hippocampus is one of the brain areas that mediate the anxiogenic effect of nicotine through enhanced 5-HT release, but the nAChR subtype(s) that mediate these effects are not known. Intrahippocampal administration of a high dose of nicotine (1 micro g, 4.3 mM) had an anxiogenic effect in the social interaction test that was reversed by co-administration of a behaviourally inactive dose (1.9 ng, 4.3 micro M) of methyllycaconitine (MLA), which is an antagonist at alpha7 and alpha3 nAChR subunits. At a dose (0.8 ng, 4.3 micro ;M) at which its actions would be specific to alpha4beta2 and alpha3beta2 nAChRs dihydro-beta-erythroidine (DHbetaE) was unable to reverse nicotine's anxiogenic effect. Reversal was obtained with a 10-fold higher, but receptor non-specific concentration of DHbetaE (7.8ng, 43 micro M), suggesting that the DHbetaE reversal might have been due to action at alpha7 nAChRs. Exposure of hippocampal slices to MLA (0.25, 05, 1 and 10 micro M) significantly reduced the increase in [(3)H]5-HT release evoked by nicotine (100 micro M). DHbetaE (0.1-0.5 micro M) failed to reverse this effect of nicotine on [(3)H]5-HT release, although higher concentrations (1 and 10 micro M), at which alpha7 subunits would also be affected, were able to do so. Because of the lack of effects of low, receptor specific concentrations of DHbetaE, it is more likely that the MLA reversal of both nicotine's anxiogenic effect and its stimulation of [(3)H]5-HT release is due to action at alpha7 than at alpha3 units. This is perhaps also more likely because the alpha7 receptors are highly expressed in the dorsal hippocampus, whereas the alpha3 subunits are much less abundant. However, what is most important is that, in the dorsal hippocampus, nicotine's anxiogenic effect and induced release of [(3)H]5-HT are mediated by non alpha4beta2 nAChRs, which contrasts with the previously reported anxiolytic effect of a low dose of nicotine which is mediated by alpha4beta2 nAChRs within the dorsal raphé nucleus. Thus the anxiolytic and anxiogenic effects of nicotine can be distinguished both by brain region and by nicotinic receptor subtype. 相似文献
17.
Previous studies have shown that adrenalectomy (ADX) increases the binding of3H-DPAT to 5-HT1A receptors in the hippocampus (HIP) and this effect is partially overcome by corticosterone (CORT) replacement. The present study investigated the time course of the effects of ADX with or without CORT replacement on serotonin (5-HT) pre- and postsynaptic systems in the HIP and dorsal raphe nucleus (DR) by quantitative autoradiography. In the HIP, ADX for 7, 10 or 14 days caused a significant increase in3H-DPAT binding in the CA1 region (pyramidal layer), CA2,3 region (molecular and pyramidal layers) and in the dentate gyrus (molecular and granular layers) which returned to control levels when measurements were made 35 days post-ADX. A decrease in3H-DPAT binding was observed 14 days after ADX in the DR but not in the median raphe nucleus (MR). Although replacement with CORT did not lead to a reversal in3H-DPAT binding at early time points, binding was restored to control levels 7–28 days after CORT replacement in all regions of the HIP. In the DR, CORT did not cause a reversal in3H-DPAT binding at any of the time points examined. In contrast to the effects seen on the 5-HT1A receptor subtype, no significant change was noted on the binding of3H-CN-IMI to uptake sites for 5-HT in the HIP or DR after ADX or CORT replacement. The results of this study indicate that long-term alterations in the HPA axis lead to changes in the 5-HT1A receptor system that are both region-specific and time-dependent. 相似文献
18.
Differential effects of centrally-active antihypertensives on 5-HT1A receptors in rat dorso-lateral septum, rat hippocampus and guinea-pig hippocampus.
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1. The electrophysiological responses elicited by 5-hydroxytryptamine1A-(5-HT1A) receptor agonists in rat and guinea-pig CA1 pyramidal neurones and rat dorso-lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2. In the presence of 1 microM tetrodotoxin (TTX), to prevent indirect effects, 5-HT, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) hyperpolarized the neurones from rat and guinea-pig brain. 3. The hypotensive drug flesinoxan, a selective 5-HT1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5-HT1A-receptors, 5-methyl-urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4. In guinea-pig hippocampal neurones, 5-methyl-urapidil behaved as a 5-HT1A-receptor antagonist. 5. The relative efficacies (5-HT = 1) of DP-5-CT, 8-OH-DPAT, flesinoxan and 5-methyl-urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea-pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6. It is concluded that the hypotensive agents flesinoxan and 5-methyl-urapidil appear to have different efficacies at 5-HT1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated. 相似文献
19.
《General pharmacology》1995,26(6):1369-1374
- 1.1. The analgesic effect of clonixinate of L-lysine (Clx) in the nociceptive C-fiber reflex in rat and in the writhing test in mice is reported.
- 2.2. Clx was administered by three routes, i.v., i.t. and i.c.v., inducing a dose-dependent antinociception.
- 3.3. The antinociceptive effect of Clx was 40–45% with respect to the control integration values in the nociceptive C-fiber reflex method.
- 4.4. The writhing test yielded ED50 values (mg/kg) of 12.0 ± 1.3 (i.p.), 1.8 ± 0.2 (i.t.) and 0.9 ± 0.1 (i.c.v.) for Clx administration.
- 5.5. Ondansetron was not able to antagonize the antinociception response of Clx in the algesiometric tests used.
- 6.6. Chlorophenilbiguanide did not produce any significative change in the analgesic effect of Clx in the nociceptive C-fiber reflex method.
- 7.7. It is suggested that the mechanism of action of the central analgesia of Clx is not mediated by 5-HT3 subtype receptors.
20.
Rationale In rodents, serotonin 1B (5-HT1B) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated
aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed
interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation.
Objective This study investigated the effects of two 5-HT1B receptor agonists on the motivation to fight and the performance of heightened aggression.
Materials and methods Male mice were housed as “residents” and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly
attack an “intruder” serving as the reinforcer. In the first experiment, the 5-HT1B receptor agonist, CP-94,253 (0–10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved
its effects via 5-HT1B receptors, the 5HT1B/1D receptor antagonist, GR 127935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the
5-HT1B agonist CP-93,129 (0–1.0 μg) was microinjected into the dorsal raphe 10 min before the FI 10 schedule.
Results The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression
towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg)
and CP-93,129 (1.0 μg) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were
less effective. GR 127935 antagonized CP-94,253’s effects on all other behaviors, except response rate.
Conclusions These data extend the anti-aggressive effects of 5-HT1B agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions
at 5-HT1B receptors in the dorsal raphe. 相似文献