Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antidepressant-like effect of the hydroalcoholic extract obtained from aerial parts of Siphocampylus verticillatus, a Brazilian medicinal plant, was investigated in two models of depression in mice and against synaptosomal uptake of serotonin, noradrenaline and dopamine. The immobility times in the forced swimming test (FST) and in the tail suspension test (TST) were significantly reduced by the extract (dose range 100-1000 mg/kg, i.p.), without accompanying changes in ambulation when assessed in an open-field. In addition when given orally the extract was also effective in reducing the immobility time in the TST. The efficacy of extract in the TST was comparable to that of the tricyclic antidepressant imipramine (15 mg/kg, i.p.) and with fluoxetine (32 mg/kg, i.p.). The anti-immobility effect of the extract (600 mg/kg, i.p.) assessed in the TST was not affected by pre-treatment with naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) or L-arginine (750 mg/kg, i.p., a nitric oxide precursor). In contrast, the extract (600 mg/kg, i.p.) antidepressant-like effect was significantly reduced by pre-treatment of animals with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis), sulpiride (50 mg/kg, i.p., a selective D2 receptor antagonist), prazosin (62.5 microg/kg, i.p., an alpha1 adrenoreceptor antagonist) or by guanosine 5'-monophosphate (GMP, 250 mg/kg, i.p., a nucleotide known to block some actions elicited by NMDA). The biochemical data show that the extract of S. verticillatus inhibited in a graded manner the uptake of monoamines. However, at the IC50 level, the extract was approximately 3.2 to 3.4-fold more potent and also more efficacious in inhibiting the synaptosomal uptake of noradrenaline and serotonin than dopamine. Taken together these data demonstrate that the extract of S. verticillatus elicited a significant antidepressant-like effect, when assessed in the TST and FST in mice. Its action seems to involve an interaction with adrenergic, dopaminergic, glutamatergic and serotonergic systems.
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PMID:Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus. 1188 77

The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.
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PMID:Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. 1270 Jun 82

The capacity of an early environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. Pregnant Sprague-Dawley rats underwent three 45-min sessions per day of prenatal restraint stress (PS) on gestation days 11-21, and their offspring were assigned to either an enriched-environment or standard living cages throughout adolescence [postnatal days (pnd) 22-43]. Juvenile rats from stressed pregnancies had a prominent depression of affiliative/playful behaviour and of basal circulating CD4 T lymphocytes, CD8 T lymphocytes and T4/T8 ratio. They also showed increased emotionality and spleen and brain frontal cortex levels of pro-inflammatory interleoukin-1beta (IL-1beta) cytokine. A more marked response to cyclophosphamide (CPA: two 2 mg/kg IP injections) induced immunosuppression was also found in prenatal stressed rats. Enriched housing increased the amount of time adolescent PS rats spent in positive species-typical behaviours (i.e. play behaviour), reduced emotionality and reverted most of immunological alterations. In addition to its effects in PS rats, enriched housing increased anti-inflammatory IL-2 and reduced pro-inflammatory IL-1beta production by activated splenocytes, also producing a marked alleviation of CPA-induced immune depression. In the brain, enriched housing increased IL-1beta values in hypothalamus, while slightly normalizing these values in the frontal cortex from PS rats. This is a first indication that an environmental intervention, such as enriched housing, during adolescence can beneficially affect basal immune parameters and rats response to both early stress and drug-induced immunosuppression.
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PMID:Beneficial effects of enriched environment on adolescent rats from stressed pregnancies. 1535 33

Effects of adenosine (Ado) and adenosine 5'-triphosphate (ATP) on the membrane potential and synaptic transmission in neurons of the rat locus coeruleus (LC) were examined, in vitro. Ado (30-300 microM) produced a hyperpolarizing response and inhibited spontaneous firing activity in neurons of the rat LC. Ado decreased input resistance of LC neurons. The Ado-induced hyperpolarization reversed polarity near the equilibrium potential of K+ (EK). Ado (100-300 microM) depressed both excitatory postsynaptic potential (EPSP) and inhibitory postsynaptic potential (IPSP). Ado (300 microM) did not alter the hyperpolarization induced by norepinephrine (30 microM). N6-Cyclopentyladenosine (CPA, 100 microM), an A1 receptor agonist, also produced a hyperpolarizing response and depressed both the EPSP and IPSP. Another A1 receptor agonist, adenosine amine congener (ADAC, 30 microM) also produced a hyperpolarizing response and consistently depressed the EPSP and IPSP. Application of ATP (100 microM) to LC neurons caused a depolarizing response associated with an increase in the firing rate of spontaneous action potential in LC neurons. The ATP-induced depolarization was accompanied by an increased input resistance and reversed polarity at--91 mV. ATP (100 microM) consistently depressed the IPSP, while it did not change the amplitude of the EPSP in a majority of neurons. alpha, beta-Methylene ATP (alpha, beta-meATP, 30 micro/M), a P2 receptor agonist, mimicked these effects of ATP. Adenosine 5'-(beta, gamma-imido) triphosphate (AMP-PNP, 100 microM), a non-metabolizable analogue of ATP, produced a depolarizing response in LC neurons, but it produced no obvious depression of the EPSP and IPSP. These results suggest that Ado and ATP cause inhibitory and excitatory modulation, respectively, of neuronal activity and synaptic transmission in the rat LC.
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PMID:Effects of adenosine and ATP on the membrane potential and synaptic transmission in neurons of the rat locus coeruleus. 1537 28

Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT1B receptor knockout mice in the TST. In contrast, male and female 5-HT1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT1B receptor knockout mice. Both male and female 5-HT1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion.
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PMID:Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice. 1568 89

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.
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PMID:Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system. 1718 64

Cordyceps sinensis (CS) has been known as a component of traditional medicines that elicit various biological effects such as anti-fatigue, immunomodulatory, and hypoglycemic actions. Since it has been well-established that fatigue is closely related to depression, we used the tail suspension test (TST) in mice to examine the antidepressant-like effects of hot water extract (HWCS) and supercritical fluid extract (SCCS) of CS. Immobility time in the TST was reduced by administration of SCCS (2.5-10 ml/kg, p.o.) dose-dependently though it was not reduced by treatment with HWCS (500-2000 mg/kg, p.o.). Neither HWCS nor SCCS altered locomotor activity in the open field test, excluding the possibility that the effect of SCCS is due to activation of locomotion. Pretreatment with prazosin (an adrenoreceptor antagonist) or sulpiride (a dopamine D2 receptor antagonist) reduced the effect of SCCS on the immobility time. In contrast, pretreatment with p-chlorophenylalanine (p-CPA, a serotonin synthesis inhibitor) did not alter the anti-immobility effect of SCCS. The last finding is consistent with an additional observation that SCCS had no effect on head twitch response induced by 5-hydroxy-L-tryptophan in mice. Taken altogether, these results suggest that SCCS may elicit an antidepressant-like effect by affecting the adrenergic and dopaminergic systems, but not by affecting the serotonergic system.
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PMID:Antidepressant-like effect of Cordyceps sinensis in the mouse tail suspension test. 1782 35

Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2'-methoxy-phenyl)-1-[2'-(n-2''-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least in part, an interaction with 5-HT(1A/1B) and 5-HT(2C) receptors.
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PMID:The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. 1794 93

Clinical studies have shown that folic acid plays a role in the pathophysiology of depression. However, very few studies have investigated its effect in behavioral models of depression. Hence, this study tested its effect in the forced swimming test (FST) and the tail suspension test (TST), two models predictive of antidepressant activity, in mice. Folic acid administered by oral route (p.o.) produced a reduction in the immobility time in the FST (50-100mg/kg) and in the TST (10-50mg/kg). The administration of folic acid by i.c.v. route also reduced the immobility time in the FST (10nmol/site) and in the TST (1-10nmol/site). Both folic acid administered by oral and i.c.v. route produced no psychostimulant effect, which indicates that its antidepressant-like effect is specific. Pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., an inhibitor of serotonin (5-HT) synthesis, for 4 consecutive days), ketanserin (5mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), prazosin (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist) or yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist) prevented the anti-immobility effect of folic acid (50mg/kg, p.o.) in the FST. Moreover, the pretreatment of mice with WAY100635 (0.1mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) blocked the decrease in immobility time in the FST elicited by folic acid (50mg/kg, p.o.), but produced a synergistic effect with a subeffective dose of folic acid (10mg/kg, p.o.). In addition, a subeffective dose of folic acid (10mg/kg, p.o.) produced a synergistic antidepressant-like effect with fluoxetine (10mg/kg, p.o.) in the FST. Overall, the results firstly indicate that folic acid produced an antidepressant-like effect in FST and in TST and that this effect appears to be mediated by an interaction with the serotonergic (5-HT(1A) and 5-HT(2A/2C) receptors) and noradrenergic (alpha(1)- and alpha(2)-adrenoceptors) systems.
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PMID:Folic acid administration produces an antidepressant-like effect in mice: evidence for the involvement of the serotonergic and noradrenergic systems. 1807 62

Depression has become of universal major importance, and it is therefore vital to expand the armamentarium for treating the condition. Lack of motivation and lassitude are major symptoms treated with the use of Marapuama (Ptychopetalum olacoides, PO) remedies by communities in the Brazilian Amazon. Considering the prominence of such symptoms in depression, the present study was designed to verify the effects of a standardized PO ethanol extract (POEE) on the forced swimming (FST) and tail suspension tests (TST). POEE i.p. (15-100 mg/kg) and oral (300 mg/kg) resulted in a significant and dose-related anti-immobility effect. We further examined the involvement of dopamine, noradrenaline and serotonin in these antidepressant-like effects. POEE effects were prevented when catecholamine synthesis was inhibited by -alpha-methyl-rho-tyrosine (AMPT) (100 mg/kg, i.p.), while inhibition of serotonin synthesis with rho-chlorophenylalanine methyl ester hydrochloride (PCPA) (100 mg/kg, i.p.) was devoid of effect. The blockade of beta-adrenergic (propranolol 2 mg/kg, i.p.) and D(1) dopamine (SCH 23390 0.5 mg/kg, i.p.) receptors prevented POEE anti-immobility effects; by contrast, blockade of D(2) dopamine (sulpiride 2 and 50 mg/kg, i.p.) receptors was ineffective. Consistent with traditional use, the results indicate that POEE possesses antidepressant-like effects, possibly mediated by beta-adrenergic and D(1) dopamine receptors.
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PMID:Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice. 1906 80


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