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 aim of this study was to determine whether sesamin, a component from Acanthopanax senticosus HARMS (ASH) pharmacologically offers protection against Parkinson's disease (PD) and its related depressive behavior in rats administered rotenone. We also examined how sesamin affected the rotenone-induced loss of tyrosine hydroxylase (TH) or glial cell line-derived neurotrophic factor (GDNF)-positive neurons in the midbrain of rats. Rats were orally administered sesamin (3, 30 mg/kg) once a day for 2 weeks before an intraperitoneal injection of rotenone (2.5 mg/kg). The pole test and catalepsy test were used to evaluate the effects of sesamin administration on bradykinesia and depressive behaviors in the PD model of rats given rotenone for 5 weeks. Those effects were compared with the ASH administrated group (250 mg/kg). Treatment with sesamin for seven weeks resulted in prophylactic effects on rotenone-induced parkinsonian bradykinesia and catalepsy, and the effects were equivalent to ASH effects. Immunohistochemistical analysis using TH or GDNF antibody showed that sesamin provided cytoprotective effects against rotenone-induced loss of DA cells. The results suggest that it may be possible to use the ASH and sesamin for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to pesticide or environmental neurotoxins in general.
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PMID:Effect of sesamin in Acanthopanax senticosus HARMS on behavioral dysfunction in rotenone-induced parkinsonian rats. 1563 86

The aim of this study was to determine whether Acanthopanax senticosus Harms (ASH) offers protection against Parkinson's disease (PD) and its related depressive behaviors in rats administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We examined how ASH affected the MPTP-induced loss of tyrosine hydroxylase (TH)-positive neurons in the midbrain of rats. Extract from the stem bark of ASH prepared with hot water was dissolved in distilled water. Rats were then orally administered ASH (250 mg/kg) once a day for 2 weeks before ASH administration plus an intraperitoneal injection of MPTP (20 mg/kg). The pole test and catalepsy test were used to evaluate the effects of ASH administration on bradykinesia and depressive behaviors in the PD model of rats given MPTP for 2 weeks. Treatment with ASH for 2 weeks resulted in prophylactic effects on MPTP-induced Parkinsonian bradykinesia and catalepsy. Immunohistochemistical analysis using TH antibody showed that ASH provided cytoprotective effects against MPTP-induced loss of dopamine (DA) cells. The present results suggest that it may be possible to use ASH for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to toxic substances.
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PMID:Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson's disease in rats. 1570 78

Depression found in Parkinson disease (PD) usually responds to selective serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C) was injected ip 30 min before H. Dunnett's test was used for comparison of means. ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found in both sexes (5 mg/kg, 180 min: ST - males: 124 +/- 10 vs 714 +/- 15 s in C; females: 116 +/- 10 vs 718 +/- 6 s in C; PX - males: 106 +/- 10 vs 714 +/- 14 s in C; females: 102 +/- 10 vs 715 +/- 14 s in C). At 0.3 mg/kg, neither of these drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the effect was not dose-dependent; no differences were observed between males and females (5 mg/kg, 180 min: males, 185 +/- 14 vs 712 +/- 14 s in C; females, 169 +/- 10 vs 710 +/- 19 s in C). For these SSRIs, maximal inhibition of NC was obtained with 5 mg/kg, 180 min after H. These results are consistent with the hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and suggest that SSRIs are possibly safe in depressive PD patients.
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PMID:Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice. 1630 1

Ketamine is known to improve opioid efficacy, reduce postoperative opioid requirement and oppose opioid associated pain hypersensitivity and tolerance. However, the mechanisms underlying these beneficial effects are not clear. This study investigated the effects of ketamine at a non-analgesic dose (30 mg/kg, i.p.) on analgesia induced by morphine (2.5, 5.0, 7.5 mg/kg, s.c.), using rat tail-flick test as an animal model of acute pain. Further, the role of opioid-, alpha2-adrenoceptors and ATP-sensitive potassium channels was examined on the potentiating effect of ketamine. Male rats received morphine alone at 5.0 and 7.5 but not at 2.5 mg/kg showed a dose-related increase in tail-flick latencies. The combination of morphine and ketamine resulted in dose-related increase in morphine analgesia, both on the intensity as well as on duration. The ketamine-induced potentiation of morphine (7.5 mg/kg) analgesia was unaffected by glibenclamide (3 mg/kg, s.c.) and only partially blocked by yohimbine (2 mg/kg, i.p.), but more completely abolished by naloxone (2 mg/kg, i.p.). Both morphine (5.0 mg/kg) and ketamine (30 mg/kg) alone did not evoke catalepsy in rats but on combination produced a synergistic effect, which was however, abolished by naloxone pretreatment. In the open-field test, while morphine (5.0 mg/kg) caused a depressant effect, ketamine (30 mg/kg) enhanced the locomotor activity. Nevertheless, in combination potentiated the morphine's depressant effect on locomotion, which was also antagonized by naloxone. These results indicate that ketamine at a non-analgesic dose can potentiate morphine analgesia, induce catalepsy and cause locomotor depression, possibly involving an opioid mechanism. This potentiation, although favorable in acute pain management, may have some adverse clinical implications.
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PMID:Ketamine-induced potentiation of morphine analgesia in rat tail-flick test: role of opioid-, alpha2-adrenoceptors and ATP-sensitive potassium channels. 1639 16

In the absence of any specific behavioral assay for cannabinoids or endocannabinoids, a cannabinoid-induced profile in a series of four in vivo assays in mice is most commonly used to assess a specific cannabinoid activity at the behavioral level. Thus, when a given compound produces motor depression in an open field, catalepsy on an elevated ring, analgesia on a hot plate, as well as hypothermia, cannabinoid CB1 receptor activation is assumed, although exceptions are possible. The full cannabinoid profile, however, includes for example ataxia in dogs and discrimination learning in rats. In view of (1) the addictive/reward potential of cannabis and the cannabinoids and (2) the multiple roles of the endocannabinoid physiological control system (EPCS) in behavioral functions, including memory, emotionality, and feeding, a number of behavioral techniques have been used to assess the effects of cannabinoids in these functions. In this chapter we will describe the tetrad of cannabinoid-induced effects as well as a series of behavioral assays used in the behavioral pharmacology of marijuana-cannabinoid research. Since the EPCS plays an important role in the developing organism, methods used in the assessment of physical and behavioral development will also be discussed. The techniques include the tetrad, drug discrimination, self-stimulation and self-administration, conditioned place preference/aversion, the plus-maze, chronic mild stress (CMS), ultrasonic vocalizations, cognitive behaviors, and developmental assessment in mouse (and rat) pups.
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PMID:Behavioral methods in cannabinoid research. 1650 14

In the present article, we review the pharmacological properties of KDS-4103 (URB597), a highly potent and selective inhibitor of the enzyme fatty-acid amide hydrolase (FAAH), which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide. In vitro, KDS-4103 inhibits FAAH activity with median inhibitory concentrations (IC(50)) of 5 nM in rat brain membranes and 3 nM in human liver microsomes. In vivo, KDS-4103 inhibits rat brain FAAH activity after intraperitoneal (i.p.) administration with a median inhibitory dose (ID(50)) of 0.15 mg/kg. The compound does not significantly interact with other cannabinoid-related targets, including cannabinoid receptors and anandamide transport, or with a broad panel of receptors, ion channels, transporters and enzymes. By i.p. administration to rats and mice KDS-4103 elicits significant, anxiolytic-like, antidepressant-like and analgesic effects, which are prevented by treatment with CB1 receptor antagonists. By contrast, at doses that significantly inhibit FAAH activity and substantially raise brain anandamide levels, KDS-4103 does not evoke classical cannabinoid-like effects (e.g., catalepsy, hypothermia, hyperphagia), does not cause place preference, and does not produce generalization to the discriminative effects of the active ingredient of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC). These findings suggest that KDS-4103 acts by enhancing the tonic actions of anandamide on a subset of CB(1) receptors, which may normally be engaged in controlling emotions and pain. KDS-4103 is orally available in rats and cynomolgus monkeys. Sub-chronic repeated dose studies (1,500 mg/kg, per os) in these two species have not demonstrated systemic toxicity. Likewise, no toxicity was noted in bacterial cytotoxicity tests in vitro and in the Ames test. Furthermore, no deficits were observed in rats on the rotarod test after acute i.p. treatment with KDS-4103 at doses up to 5 mg/kg or in a functional observation battery after oral doses up to 1,500 mg/kg. The results suggest that KDS-4103 will offer a novel approach with a favorable therapeutic window for the treatment of anxiety, depression and pain.
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PMID:Pharmacological profile of the selective FAAH inhibitor KDS-4103 (URB597). 1683 56

The sensory contact model can induce various different psychopathological states in male mice (anxious depression, catalepsy, social withdrawal, pathological aggression, cognition disturbances, anhedonia, alcoholism etc.). Additionally, this model facilitates the screening of drugs for therapeutic properties, preventive properties and efficiency under simulated clinical conditions. This approach can reveal the action of drugs at different stages of disease development. It is proposed that this pharmacological approach can be applied for the screening of various novel psychotropic drugs.
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PMID:An experimental approach for the study of psychotropic drug effects under simulated clinical conditions. 1847 54

Thyroxine synthesis inhibitors produced augmentation in predisposition to catalepsy and a decrease of sexual motivation and acoustic startle reflex response in rat. Sensitivity of these behavioral alterations to antidepressants was unknown. Chronic treatment with prototypical antidepressant imipramine (15 mg/kg, 21 days) prevented manifestation of catalepsy expression and sexual motivation reduction in Wistar rats given propylthiouracil (50 mg/l, 28 days) but did not influence startle reflex amplitude. Behavioral recovery induced by imipramine did not attribute to alterations in locomotor activity in open-field test or body weight gain. 5-HT(2A)-receptor mRNA level in the frontal cortex was not changed either. Model of sexual motivation disturbance and catalepsy induced by propylthiouracil in rat seems to be prospective to study the role of thyroid dysfunctions in mechanisms of depression and antidepressant treatment.
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PMID:[Chronic imipramine treatment normalizes decreased sexual motivation and high predisposition to catalepsy induced by propylthiouracil in rat]. 1866 84

The passive avoidance learning and extinction in mice strain ASC with high predisposition to catalepsy as compared with mice of CBA and AKR strains were analyzed. Impairment of fear extinction as a major symptom of depression was revealed in ASC mice, whereas a delay of extinction in CBA mice and fast formation of new inhibitory learning in AKR mice were found. It is suggested that the long persistence of fear in ASC mice results from increased anxiety during the repeated presentation of a context in the absent of aversive stimulus. Defect of fear inhibition in ASC mice makes it possible to use this strain of mice as genetic model of depression.
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PMID:[Learning and extinction of passive avoidance in mice with high predisposition to catalepsy]. 1872 70

Thyroxine synthesis inhibitors increase the predisposition to catalepsy and decrease sexual motivation and the amplitude of the acoustic startle reflex in rats. The sensitivity of these behavioral changes to antidepressants remains uncertain. Chronic administration of the classical tricyclic antidepressant imipramine (15 mg/kg, 21 days) prevented the appearance of high sensitivity to catalepsy and the decrease in sexual motivation in Wistar rats given propylthiouracil (50 mg/liter, 28 days), without altering the amplitude of the startle reflex. Normalization of behavior in response to imipramine was not associated with changes in movement activity in the open field test or the animals' body weight. There was also no change in the expression of the 5-HT2A serotonin receptor gene in the frontal cortex. The model of propylthiouracilinduced catalepsy with reduced sexual motivation in rats has potential for studying the role of thyroid abnormalities in the development of depression and the mechanisms of action of antidepressants.
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PMID:Chronic administration of imipramine normalizes decreased sexual motivation and increased predisposition to catalepsy induced by propylthiouracil in rats. 1934 May 85


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