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1.
DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] displays a high affinity for the rat 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi 7.3, 7.4 and 7.8, respectively) and acts as an agonist. DOI (0.5-4 mg/kg, i.p. 30 min pre-test) increased the number of punished passages in the mouse four plates test (FPT). The anti-punishment action of DOI (1 mg/kg, i.p. 30 min pre-test) was abolished by prior treatment with the selective 5-HT2A receptor antagonist SR 46949B (0.1 and 1 mg/kg, i.p. 45 min pre-test) but not by the selective 5-HT2C receptor antagonist RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor the selective 5-HT2C/2B receptor antagonist SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). An anxiolytic-like action was also observed for DOI (1 mg/kg) in the elevated plus maze (EPM). The anxiolytic-like action of DOI (1 mg/kg, i.p. 30 min pre-test) was antagonised by pre-treatment with SR 46949B (0.125 and 0.5 mg/kg, i.p. 45 min pre-test) but not by RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). In conclusion, DOI produced an anxiolytic-like profile in the mouse FPT and EPM. These effects are likely to be 5-HT2A receptor mediated. 相似文献
2.
Machado DG Kaster MP Binfaré RW Dias M Santos AR Pizzolatti MG Brighente IM Rodrigues AL 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(2):421-428
Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level. 相似文献
3.
Duarte FS Lach G Martins PR Romeiro GA de Lima TC 《Progress in neuro-psychopharmacology & biological psychiatry》2008,32(2):368-374
Our previous study described the synthesis of 4-amine derivatives of 10,11-dihydro-5H-dibenzo-alkylamine-cycloheptane, 4-amine (3-N,N-dimethylpropylamine)-10,11-dihydro-5H-dibenzo[a,d] cycloheptane-5-one (ADDCH1), and 1,2,3,4,8,9-hexahydro-dibenzocycloheptane[4,4a,5-ef]1,4-diazepin (ADDCH2), and the characterization of their antidepressant-like effect in the forced swimming test in mice. This study investigated the involvement of monoaminergic pathways in the antidepressant-like effect of these compounds in mice evaluated in the tail suspension test (TST), another animal model to screen antidepressant drugs. Our results show that the immobility time in the TST was significantly reduced by ADDCH1 (15 to 50 mg/kg, i.p.) or ADDCH2 (30 and 50 mg/kg, i.p.). The antidepressant-like effect of ADDCH1 (30 mg/kg, i.p.) in the TST was prevented by pre-treatment of mice with methysergide (2 mg/kg, i.p.), a non-selective serotonin receptor antagonist, p-chlorophenylalanine methylester (pCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis, prazosin (62.5 microg/kg, i.p.), an alpha1-adrenoceptor antagonist, or yohimbine (1 mg/kg, i.p.), an alpha2-adrenoceptor antagonist. In contrast, the antidepressant-like effect of ADDCH2 was antagonized only by yohimbine (1 mg/kg) or haloperidol (50 microg/kg, i.p.), a dopamine D2/D3/D4 receptor antagonist, and was not affected by methysergide, pCPA or prazosin. Altogether, the present results strongly suggest the differential involvement of monoaminergic systems, serotonin/noradrenaline (ADDCH1) and noradrenaline/dopamine (ADDCH2) pathways, respectively, in the antidepressant-like effect of dibenzosuberone compounds. 相似文献
4.
Kojima T Matsumoto M Togashi H Tachibana K Kemmotsu O Yoshioka M 《Brain research》2003,959(1):165-168
A selective 5-HT reuptake inhibitor, fluvoxamine (10 and 30 mg/kg, i.p.) suppressed long-term potentiation (LTP) in the hippocampal CA1 field of anesthetized rats. Fluvoxamine (30 mg/kg, i.p.)-induced suppression of LTP was completely reversed by the 5-HT(1A) receptor antagonist NAN-190 (0.5 mg/kg, i.p), but not by the 5-HT(4) receptor antagonist GR 113808 (20 microg/rat, i.c.v.) and the 5-HT(7) receptor antagonist DR 4004 (10 microg/rat, i.c.v.). These data suggest that the inhibitory effect of fluvoxamine on LTP induction is mediated via 5-HT(1A) receptors. 相似文献
5.
Chandra C. Cardoso Kelly R. Lobato Ricardo W. Binfaré Priscilla K. Ferreira Angelo O. Rosa Adair Roberto S. Santos Ana Lúcia S. Rodrigues 《Progress in neuro-psychopharmacology & biological psychiatry》2009
Literature data has shown that acute administration of magnesium reduces immobility time in the mouse forced swimming test (FST), which suggests potential antidepressant activity in humans. However, its mechanism of action is not completely understood. Thus, this study is aimed at investigating the antidepressant-like action of magnesium and the possible involvement of the monoaminergic system in its effect in the FST. The immobility time in the FST was significantly reduced by magnesium chloride administration (30–100 mg/kg, i.p.) without accompanying changes in ambulation when assessed in an open-field test. The pre-treatment of mice with NAN-190 (0.5 mg/kg, i.p. a 5-HT1A receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist), ritanserin (4 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ketanserin (5 mg/kg, a preferential 5-HT2A receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), haloperidol (0.2 mg/kg, i.p., a non selective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist) 30 min before the administration of magnesium chloride (30 mg/kg, i.p.) significantly prevented its anti-immobility effect in the FST. Moreover, the administration of sub-effective doses of fluoxetine (10 mg/kg, i.p., serotonin reuptake inhibitor), imipramine (5 mg/kg, i.p., a mixed serotonergic noradrenergic reuptake inhibitor), bupropion (1 mg/kg, i.p., dopamine reuptake inhibitor) was able to potentiate the action of sub-effective doses of magnesium chloride. In conclusion, the present study provides evidence indicating that the antidepressant-like effect of magnesium in the FST is dependent on its interaction with the serotonergic (5-HT1A and 5-HT2A/2C receptors), noradrenergic (α1- and α2- receptors) and dopaminergic (dopamine D1 and D2 receptors) systems. 相似文献
6.
Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test 总被引:4,自引:0,他引:4
Dias Elpo Zomkowski A Oscar Rosa A Lin J Santos AR Calixto JB Lúcia Severo Rodrigues A 《Brain research》2004,1023(2):253-263
This study investigated the involvement of 5-HT(1) and 5-HT(2) receptors in the antidepressant-like effect of agmatine in the mouse forced swimming test (FST). Pretreatment with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, intraperitoneally (i.p.), an inhibitor of serotonin synthesis, for 4 consecutive days), methysergide (5 mg/kg, i.p., a serotonin (5-HT) antagonist), pindolol (32 mg/kg, i.p., a 5-HT(1A/1B) receptor/beta-adrenoceptor antagonist), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridynyl)cyclohexanecarboxamide (WAY 100635; 0.3 mg/kg, subcutaneously (s.c.), a selective 5-HT(1A) receptor antagonist), 1-(2-methoxyphenyl)-4[-(2-phthalimido)butyl]piperazine) (NAN-190; 0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane; 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist), cyproheptadine (3 mg/kg, i.p., a 5-HT(2) antagonist) or ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with propranolol (2 mg/kg, i.p., a beta-adrenoceptor antagonist), prevented the effect of agmatine (10 mg/kg, i.p.) in the FST. A subeffective dose of agmatine (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with pindolol (32 mg/kg), NAN-190 (0.5 mg/kg, i.p.), WAY 100635 (0.03 mg/kg, s.c.), (+)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT; 0.01 mg/kg, i.p., a 5-HT(1A) receptor agonist), R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI; 1 mg/kg, i.p., a preferential 5-HT(2A) receptor agonist), or fluoxetine (10 mg/kg, i.p., a selective serotonin reuptake inhibitor, SSRI) but not with isamoltane (2.5 mg/kg, i.p.), ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or ketanserin (5 mg/kg, i.p.). Taken together, the results firstly demonstrate that agmatine antidepressant-like effects in the FST seem to be mediated, at least in part, by an interaction with 5-HT(1A/1B) and 5-HT(2) receptors. 相似文献
7.
Brüning CA Prigol M Luchese C Pinton S Nogueira CW 《Progress in neuro-psychopharmacology & biological psychiatry》2012,38(2):168-174
Bipolar disorder (BD) is a common and severe mood disorder associated with higher rates of suicide and disability. Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces behavioral changes in rats and has been used as a model of mania. The aim of this study was to investigate if diphenyl diselenide [(PhSe)(2)], an organoselenium compound with pharmacological properties, is effective against ouabain-induced hyperactivity and alterations in cerebral oxidative status of rats. Male Wistar rats were treated with a single dose of (PhSe)(2) (50 mg/kg, p.o.) 30 min before i.c.v. injection of ouabain (5 μl, 10(-5) M) or with the mood stabilizer, lithium chloride (LiCl) (45 mg/kg, p.o.), twice a day, for 7 days before the administration of ouabain. Open-field locomotion was quantified after ouabain administration. Thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, tyrosine nitration, ascorbic acid and non-protein thiols (NPSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in the whole brain. Ouabain increased locomotor activity in the open-field test and pretreatment with (PhSe)(2) or LiCl blocked this effect. In addition, ouabain increased lipid peroxidation and oxidatively modified proteins, demonstrated by a significant increase in TBARS levels and carbonyl content, which were attenuated by pretreatment with (PhSe)(2) or LiCl. The activities of SOD and CAT were increased by ouabain. LiCl was effective on preventing the increases of both enzyme activities, but (PhSe)(2) attenuated the ouabain effect in SOD activity. GPx and GR activities, ascorbic acid, NPSH and tyrosine nitration levels were not altered in all experimental groups. Similarly to LiCl, (PhSe)(2) produced an antimanic-like action, since it was effective against the locomotor hyperactivity elicited by ouabain. The results also indicated that (PhSe)(2) was effective against oxidative stress caused by ouabain in rats. 相似文献
8.
Poleszak E Socała K Szopa A Wróbel A Szewczyk B Kasperek R Blicharska E Nowak G Wlaź P 《Journal of neural transmission (Vienna, Austria : 1996)》2011,118(6):857-864
In the present study, we demonstrated that low, ineffective doses of N-methyl-d-aspartic acid (NMDA) receptor antagonists [competitive NMDA antagonist, CGP 37849, at 0.312 mg/kg intraperitoneally (i.p.),
antagonist of the glycineB sites, L-701,324, at 2 mg/kg i.p., partial agonist of glycineB sites, d-cycloserine, at 2.5 mg/kg i.p.] administered jointly with an ineffective dose of the benzodiazepine, chlordiazepoxide (CDP,
2.5 mg/kg i.p.), significantly increased the percentage of time spent in the open arms of the elevated plus-maze (index of
anxiolytic effect). Furthermore, CDP-induced anxiolytic-like activity (5 mg/kg i.p.) was antagonized by NMDA (75 mg/kg i.p.)
and by an agonist of glycineB sites of the NMDA receptor complex, d-serine [100 nmol/mouse intracerebroventricularly (i.c.v.)]. The present study showed a positive interaction between γ-aminobutyric
acid (GABA) and glutamate neurotransmission in the anxiolytic-like activity in the elevated plus-maze test in mice and this
activity seems to particularly involve the NMDA receptors. 相似文献
9.
Csar Augusto Brüning Marina Prigol Juliano A. Roehrs Cristina Wayne Nogueira Gilson Zeni 《Behavioural brain research》2009,205(2):145
The organoselenium compound diphenyl diselenide (PhSe)2 has shown interesting antioxidant and neuroprotective activities. On the other hand, this compound has also presented some toxic effects. m-Trifluoromethyl-diphenyl diselenide (m–CF3–C6H4Se)2, a structural analog of (PhSe)2, has proven to be antipsychotic and antioxidant in mice. The present study was designed to investigate the anxiolytic-like effect of (m–CF3–C6H4Se)2 in female mice, employing light/dark box and elevated plus-maze (EPM) tests. The involvement of 5-hydroxytryptamine (5-HT) receptors and monoamine oxidase (MAO) activity in the anxiolytic-like effect was also evaluated. (m–CF3–C6H4Se)2 (0.1, 10 and 100 mg/kg, p.o.) did not affect locomotor activity as evaluated in the open-field test (OFT). (m–CF3–C6H4Se)2 at the dose of 100 mg/kg produced an anxiolytic-like action, both in light–dark box and the EPM tests. To evaluate the role of 5-HT receptors in the anxiolytic-like effect of (m–CF3–C6H4Se)2, a selective 5-HT1A receptor antagonist, WAY100635 (0.1 mg/kg, s.c.), a non-selective 5-HT2A/2C receptor antagonist, ritanserin (2 mg/kg, i.p.) and a selective 5-HT3 receptor antagonist, ondansetron (0.1 mg/kg, i.p.) were used. All the antagonists used were able to abolish the anxiolytic-like effect of (m–CF3–C6H4Se)2. (m–CF3–C6H4Se)2, at the dose of 100 mg/kg, inhibited the MAO-A activity in mice brain. Taken together these data demonstrated that the anxiolytic-like effect caused by (m–CF3–C6H4Se)2 seems to be mediated by the involvement of the serotonergic system. 相似文献
10.
Andiara E. Freitas Josiane Budni Kelly R. Lobato Ricardo W. Binfaré Daniele G. Machado Jardel Jacinto Patrícia O. Veronezi Moacir G. Pizzolatti Ana Lúcia S. Rodrigues 《Progress in neuro-psychopharmacology & biological psychiatry》2010
The antidepressant-like effect of the ethanolic extract obtained from barks of Tabebuia avellanedae, a plant widely employed in folk medicine, was investigated in two predictive models of depression: forced swimming test (FST) and tail suspension test (TST) in mice. Additionally, the mechanisms involved in this antidepressant-like action and the effects of the association of the extract with the antidepressants fluoxetine, desipramine and bupropion in the TST were investigated. The extract from T. avellanedae produced an antidepressant-like effect, in the FST (100 mg/kg, p.o.) and in the TST (10–300 mg/kg, p.o.), without accompanying changes in ambulation when assessed in the open-field test. The anti-immobility effect of the extract (30 mg/kg, p.o.) in the TST was prevented by pre-treatment of mice with ketanserin (5 mg/kg, i.p., a preferential 5-HT2A receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist) and SCH23390 (0.05 mg/kg, s.c., a dopamine D1 receptor antagonist). The combined administration of a subeffective dose of WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist) and a subeffective dose of the extract (1 mg/kg, p.o.) produced a significant reduction in the immobility time in the TST. In addition, the combination of fluoxetine (1 mg/kg, p.o.), desipramine (0.1 mg/kg, p.o.), or bupropion (1 mg/kg, p.o.) with a subeffective dose of the extract (1 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing hyperlocomotion in the open-field test. It may be concluded that the extract from T. avellanedae produces an antidepressant-like effect in the FST and in the TST that is dependent on the monoaminergic system. Taken together, our results suggest that T. avellanedae deserves further investigation as a putative alternative therapeutic tool that could help the conventional pharmacotherapy of depression. 相似文献
11.
Post traumatic stress disorder (PTSD) is characterised by hyperarousal, anxiety and amnesic symptoms. Deficits in explicit memory recall have been causally related to volume reductions of the hippocampus and prefrontal cortex. While stress-related glucocorticoid secretion appears involved in this apparent atrophy, there is also evidence for low plasma cortisol in PTSD. Prior exposure to trauma is an important risk factor for PTSD, suggesting a role for sensitisation. Using Sprague-Dawley rats, we studied the effects of a time-dependent sensitisation (TDS) model of stress on spatial memory deficits, 1 week post-stress, using the Morris water maze. Basal and 7-day post-stress plasma corticosterone levels were also determined. Due to the putative role of serotonin in anxiety and stress, and in the treatment of PTSD, hippocampal 5HT(1A) and prefrontal cortex 5HT(2A) radioligand binding studies were performed. TDS stress evoked a marked deficit in spatial memory on day 7 post TDS stress, coupled with significantly depressed plasma corticosterone levels. Cognitive and endocrine changes at day 7 post stress were associated with a significant increase in receptor density (B(max)) and a significant decrease in receptor affinity (K(d)) for hippocampal 5HT(1A) receptors. The B(max) of prefrontal cortex 5HT(2A) receptors were unaffected, but K(d) was significantly increased. We conclude that TDS stress evokes cognitive and endocrine changes characteristic of PTSD. Moreover, TDS stress induces diverse adaptive 5HT receptor changes in critical brain areas involved in emotion and memory that may underlie the effect of stress on cognitive function. 相似文献
12.
Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function. 相似文献
13.
5HT1A receptor antagonists enhance the functional activity of fluoxetine in a mouse model of feeding
Fluoxetine has been reported to suppress food intake in animal models of feeding. Fluoxetine increases extracellular serotonin in the brain. 5HT1A autoreceptors regulate synaptic levels of serotonin. A combination of a 5HT1A receptor antagonist and fluoxetine has been previously reported to enhance extracellular levels of serotonin over what is obtained with fluoxetine alone. Thus, a combination of fluoxetine and a 5HT1A antagonist could enhance the ability of fluoxetine to suppress appetite. Fluoxetine was tested in a model of feeding, in which CD-1 mice were trained to drink sweetened condensed milk. Fluoxetine was found to attenuate milk drinking, in a dose-dependent manner, at doses greater than 10 mg/kg, i.p. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, was then combined either with 5-hydroxytryptophan (5HTP), a serotonin precursor, or with S(−) pindolol, a 5HT1A/β adrenergic receptor antagonist or with LY206130, a more selective 5HT1A receptor antagonist. These treatment paradigms resulted in significant attenuation of the consumption of sweetened condensed milk. Since fluoxetine has been shown to be useful in the treatment of eating disorders and to promote weight loss in obese humans, although at doses greater than those required for the treatment of depression, a combination of fluoxetine with a 5HT1A receptor antagonist could be of clinical utility in the treatment of eating disorders and obesity. 相似文献
14.
Rosa AO Kaster MP Binfaré RW Morales S Martín-Aparicio E Navarro-Rico ML Martinez A Medina M García AG López MG Rodrigues AL 《Progress in neuro-psychopharmacology & biological psychiatry》2008,32(6):1549-1556
Glycogen synthase kinase-3beta (GSK-3beta) is an enzyme that phosphorylates glycogen synthase, thereby inhibiting glycogen synthesis. Besides this role, it is now believed that this enzyme plays an important role in the pathophysiology of many brain diseases including depression. Some inhibitors of this enzyme have shown antidepressant effects in animal models. This study investigated the effects of a novel thiadiazolidinone NP031115, a putative GSK-3beta inhibitor, and the well-established GSK-3beta inhibitor AR-A014418 in the mouse forced swimming test (FST), a model widely used to evaluate antidepressant activity. We found that NP031115 had an IC50 of 1.23 and 6.5 microM for GSK-3beta and GSK-3alpha, respectively. NP031115 (0.5 and 5 mg/kg, i.p.), in a way similar to imipramine (15 mg/kg, i.p), fluoxetine (32 mg/kg, i.p), AR-A014418 (9 mg/kg, i.p.), and rosiglitazone (5 microg/site, i.c.v.), significantly reduced immobility time in the FST. NP031115 at the higher dose and AR-A014418 (9 mg/kg, i.p.) reduced locomotion in the open-field test. Rosiglitazone (30 microM), AR-A014418 (1 microM), PG(J2) (10 microM), and NP031115 (1, 10 and 25 microM) activate PPARgamma in CHO transfected cells. GW-9662 (10 microg/site, i.c.v, a PPARgamma antagonist) administered 15 min before NP03115 (5 mg/kg, i.p.) or co-administered with rosiglitazone (5 microg/site, i.c.v.) prevented the antidepressant-like effect of these drugs in the FST. The results of this study show that NP031115 can exhibit an antidepressant effect, likely by inhibiting GSK-3beta and enhancing PPARgamma activity. 相似文献
15.
《Neurological research》2013,35(9):1002-1008
Abstract Objectives: The involvement of the GABAergic system in seizures induced by diphenyl diselenide (PhSe)2 in rat pups was investigated. Methods: To this end, the effect of aminooxyacetic acid hemihydrochloride (AOAA, 20 mg/kg; by intraperitoneal route, i.p.), a GABA-T inhibitor; DL-2,4-diamino-n-butyric acid hydrochloride (DABA, 16 mg/kg; i.p.), an inhibitor of GABA uptake; and γ-aminobutyric acid (GABA, 10 and 40 mg/kg; i.p.), diazepam (3 mg/kg; i.p.) and phenobarbital (40 mg/kg; i.p.), GABAergic agonists as well as picrotoxin (1 mg/kg; i.p.), a GABAA receptor antagonist on (PhSe)2 (50 and 500 mg/kg, by oral route, p.o.)-induced seizures, were studied. The [3H]GABA uptake levels by cortical and hippocampal slices in rat pups exposed to (PhSe)2 were also carried out. Results: Pre-treatment with GABA (40 mg/kg), diazepam, phenobarbital, AOAA and DABA abolished the appearance of seizures induced by 50 mg/kg (PhSe)2 in rat pups. Picrotoxin increased the percentage of convulsing rat pups from 42 to 100% and reduced significantly the onset for the first convulsive episode induced by (PhSe)2 at the dose of 50 mg/kg. Diazepam and phenobarbital prolonged significantly the latency for the onset of the first convulsive episode caused by 500 mg/kg (PhSe)2 in rat pups. [3H]GABA uptake levels were stimulated in cerebral cortical and hippocampal slices of convulsing rat pups administered with both doses of (PhSe)2. Discussion: Our findings demonstrated that seizures induced by (PhSe)2 are mediated, at least in part, by an interaction with GABAergic system. 相似文献
16.
Müller LG Salles LA Stein AC Betti AH Sakamoto S Cassel E Vargas RF von Poser GL Rates SM 《Progress in neuro-psychopharmacology & biological psychiatry》2012,36(1):101-109
The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased mice immobility in the FST (0.5-20 mg/kg p.o.) and elicited a biphasic dose-response relationship in the TST (1-20 mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5 mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1 mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15 μg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50 mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1 mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4 × 100 mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25 mg/kg) and imipramine (10 mg/kg), desipramine (5 mg/kg) and bupropion (3 mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission. 相似文献
17.
This study investigated the involvement of 5-HT1 and 5-HT2 receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test (FST). The pre-treatment of mice with PCPA (100mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5mg/kg, i.p., a 5-HT1A receptor antagonist), pindolol (32 mg/kg, i.p., a 5-HT1A/1B receptor/beta-adrenoceptor antagonist) or WAY100635 (0.1 and 0.3mg/kg, s.c., a selective 5-HT1A receptor antagonist), but not with ketanserin (5mg/kg, i.p., a 5-HT2A/2C receptor antagonist), prevented the antidepressant-like effect of adenosine (10mg/kg, i.p.) in the FST. Moreover, the pre-treatment of animals with WAY100635 (0.1mg/kg, s.c.) blocked the decrease in immobility time in the FST elicited by adenosine (5 or 10mg/kg, i.p.), but produced a synergistic effect with a sub-effective dose of adenosine (1mg/kg, i.p.) and did not cause any alteration at the highest dose of adenosine administered (50mg/kg, i.p.). Adenosine (1mg/kg, i.p.) produced a synergistic antidepressant-like effect with pindolol (32 mg/kg), NAN-190 (0.5mg/kg, i.p.), WAY100635 (0.03 mg/kg, s.c.), 8-OH-DPAT (1mg/kg, i.p., a 5-HT1A receptor agonist), but not with DOI (1mg/kg, i.p., a preferential 5-HT2A receptor agonist) or ketanserin. The pre-treatment of mice with DPCPX (2mg/kg, i.p., a selective adenosine A1 receptor antagonist) or ZM241385 (1mg/kg, i.p., a selective adenosine A2A receptor antagonist) did not prevent the effect of fluoxetine (32 mg/kg, i.p., a preferential serotonin reuptake inhibitor) in the FST. Besides that, adenosine (1mg/kg, i.p.) did not produce a synergistic antidepressant-like effect with fluoxetine (10mg/kg, i.p.). Taken together, the results indicate that the antidepressant-like effect of adenosine in the FST appears to be mediated, at least in part, by an interaction with 5-HT1A receptors. 相似文献
18.
In the present study, we investigated effects of the new selective adenosine A2A receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) on L-DOPA-induced dopamine (DA) release in the striatum of intact and reserpine-treated rats. CSC given in a pharmacologically effective dose of 5 mg/kg i.p. significantly increased striatal DA release after joint administration of L-DOPA (100 mg/kg, i.p.) and benserazide (50 mg/kg, i.p.) to intact and reserpine (2.5 mg/kg, s.c.)-injected rats. CSC did not change the elevated level of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in intact rats, but raised it in DA-depleted animals. The availability of exogenous L-DOPA in the extracellular space was similar and equally increased by CSC in both intact and reserpinized rats. Our results suggest that the observed effects may be mediated by striatal adenosine A2A receptors, and are probably related to the CSC action on DA metabolism and the increased transport of exogenous L-DOPA into the brain. These observations might be of relevance, considering the use of selective A2A antagonists as potential supplements to L-DOPA therapy of Parkinson's disease. 相似文献
19.
Morris HV Dawson GR Reynolds DS Atack JR Stephens DN 《The European journal of neuroscience》2006,23(9):2495-2504
Mice with point-mutated alpha2 GABAA receptor subunits (rendering them diazepam insensitive) are resistant to the anxiolytic-like effects of benzodiazepines (BZs) in unconditioned models of anxiety. We investigated the role of the alpha2 GABAA subtype in a model of conditioned anxiety. alpha2(H101R) and wildtype mice were trained in a conditioned emotional response (CER) task, in which lever-pressing for food on a variable interval (VI) schedule was suppressed during the presentation of a conditioned stimulus (CS+) that predicted footshock. The ability of diazepam, ethanol and pentobarbital to reduce suppression during the CS+ was interpreted as an anxiolytic response. Diazepam (0, 0.5, 1, 2, 4 and 8 mg/kg) induced a dose-dependent anxiolytic-like effect in wildtype mice. At high doses, diazepam (2, 4 and 8 mg/kg) was sedative in alpha2(H101R) mice. Analysis of the anxiolytic properties of nonsedative diazepam doses (0.5 and 1 mg/kg), showed that alpha2(H101R) mice were resistant to the anxiolytic effects of diazepam. Equivalent anxiolytic properties of pentobarbital (20 mg/kg) and ethanol (1 and 2 g/kg) were seen in both genotypes. These findings confirm the critical importance of the alpha2 GABAA subtype in mediating BZ anxiolysis. However, as a compound, L-838417, with agonist properties at alpha2, alpha3 and alpha5-containing receptors, gave rise to anxiolytic-like activity in alpha2(H101R) mice in the CER test, alpha3-containing GABA receptors are also likely to contribute to anxiolysis. Observations that alpha2(H101R) mice were more active, and displayed a greater suppression of lever pressing in response to fear-conditioned stimuli than wildtype mice, suggests that the alpha2(H101R) mutation may not be behaviourally silent. 相似文献
20.
The behavioural effects of 5-HT2 receptor agonists, 5-HT2A and 5-HT2C receptor antagonists were investigated in the mouse four plates test (FPT), light/dark paradigm (L/D) and the elevated plus maze (EPM), in order to elucidate the role of the 5-HT2 receptor subtypes in these models and to address the inconclusive results previously reported using rat psychopharmacological models. All compounds were administered intraperitoneally 30 min before each test. DOI, a preferential 5-HT2A agonist (0.5–8 mg/kg) and BW 723C86, a 5-HT2B agonist (8 and 16 mg/kg) provoked an anxiolytic-like response in the FPT. In the EPM, an anxiolytic-like effect was observed for DOI (0.5, 1 and 2 mg/kg), BW 723C86 (0.5, 4, 8 and 16 mg/kg), RO 60-0175 a 5-HT2C agonist (4 mg/kg) and the non-selective 5-HT2 receptor agonist mCPP (0.25 mg/kg.). Ketanserin, a 5-HT2A/2C non-selective receptor antagonist (0.015 and 0.03 mg/kg), induced an anxiogenic-like effect in the L/D paradigm. The 5-HT2C antagonists (RS 10-2221, SDZ SER082 and SB 206553) were without effect in all three tests. These behavioural results are indicative of an anxiolytic-like action of 5-HT2 receptor agonists, an anxiogenic-like effect of 5-HT2A receptor antagonism, whereas the blockade of 5-HT2C receptors are without effect in the mouse models studied. 相似文献