Search results for "Reuptake"
showing 10 items of 96 documents
Behavioral analysis indicates benzodiazepine-tolerance mediated by the benzodiazepine binding-site at the GABA(A)-receptor.
2001
Abstract 1. GABA A -receptor induced changes in locomotion and anxiety-like behaviors were studied in rats using an open-field and an elevated plus-maze. Acute and chronic doses of the benzodiazepine diazepam without and in combination with the GABA uptake inhibitor SKF-89976A were investigated. 2. Fifty-six male rats of the strain PVG/OlaHsd (PVG; 180–200g body wt) were used to assess the influence of the benzodiazepine binding-site to the development of tolerance. Rats were divided into six groups: The first receiving saline (0.9%), the second and third diazepam (10.0 mg/kg) daily for 23 days with or without an acute challenge of 2.0 mg/kg diazepam. The fourth group received diazepam (10.…
Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze.
2002
Abstract γ-Amino-butyric acid (GABA) is cleaved from the synaptic cleft by uptake via specific transporters. Inhibition of such transporters increases the effectiveness of physiologically released GABA. Increased GABAergic neurotransmission has an impact on learning and memory. Therefore, effects of tiagabine, a GABA-transporter inhibitor, were investigated on spatial orientation in the Morris water-maze. Rats were given four training trials per day for 4 days and a probe trial without platform on the 5th day. Compared to saline treated rats, rats treated daily with 20 mg/kg tiagabine showed impaired learning during the acquisition trials. Retrieval was impaired in rats treated only at the …
Role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat
2021
The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting th…
Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein
2010
According to in vitro studies the enantiomers of venlafaxine display different degrees of serotonin and noradrenaline reuptake inhibition. Therefore, clarification of the enantiomeric drug distribution between serum and brain is highly warranted. To elucidate if P-glycoprotein (P-gp) in a stereoselective manner transports venlafaxine and its metabolites out of the brain we used abcb1ab double-knockout mice that do not express P-gp. A single dose of racemic venlafaxine (10 mg/kg bw) was intraperitoneally injected to knockout (-/-) and wildtype (+/+) mice. Serum and brain samples were collected 1, 3, 6 and 9 h following drug administration for analysis by LC/MS/MS. One to six hours post-dose,…
Treatments used for obsessive-compulsive disorder-An international perspective.
2018
Objective The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive–compulsive disorder (OCD). Methods Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. Results The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13…
Effects of acute and chronic maprotiline administration on inhibitory avoidance in male mice
2000
The effects of acute and chronic administration of maprotiline (5, 10 or 20 mg/kg, intraperitoneally) were assessed on inhibitory avoidance in male mice. Acute administration of maprotiline before training did not effect training phase latencies, but impaired performance (i.e. produced shorter latencies) in the test at doses of 5 and 20 mg/kg. When given after training, the drug did not modify test latencies at any of the doses used. Chronic administration for 21 days (interrupted 24 h before training) also shortened latencies in the test but not in training. An experiment on the acute effects of maprotiline on analgesia (determination of flinch and jump thresholds for increasing electric f…
The pathogenetic role of adulterants in 5 cases of drug addicts with a fatal outcome
2013
The purpose of the present study is to determine the role of lidocaine, caffeine and dextromethorphan, used as adulterant substances, in five cases of drug overdose which have come to our attention. Taking into account the pharmacological mechanism, blood concentration and route of administration (intravenous) we evaluated the hypothesis that these substances could act with a synergistic effect - or at least additive - with the illicit drugs on the central nervous system and cardiovascular system.
Risk of bleeding related to selective and non-selective serotonergic antidepressants: a case/non-case approach using data from two pharmacovigilance …
2014
There is increasing evidence for an association between treatment with selective serotonin reuptake inhibitors (SSRI) and an increased risk of bleeding events. The most important underlying mechanism appears to be inhibition of serotonin uptake in platelets, an effect that is also present in antidepressants with non-selective serotonin-reuptake inhibition (NSRI). Accordingly, also NSRI may be associated with an increased risk of bleeding. However, there is little data in this regard.Based on data (spontaneous reports of adverse drug reactions) from 2 pharmacovigilance databases (WHO-database/Vigibase™; BfArM/AkdÄ-database in Germany) we used a case/non-case approach and calculated reporting…
Neurochemical Substrates of MDMA Reward: Effects of the Inhibition of Serotonin Reuptake on the Acquisition and Reinstatement of MDMA-induced CPP
2013
Different neurotransmitter brain systems have been implicated in the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA), including dopamine or serotonin. Serotonin selective reuptake inhibitors (SSRI) are a commonly prescribed therapy for psychiatric disorders, and the SSRI fluoxetine is recommended for MDMA users due to its neuroprotective effect against MDMAinduced neurotoxicity. In the present work, we employed the conditioned place preference (CPP) paradigm to study how the inhibition of serotonin reuptake with fluoxetine affected the rewarding and reinstating effects of MDMA in adolescent male mice. Firstly, we evaluated the motivational effects of fluoxetine (1 and 10 mg/kg)…
Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat
2007
Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-re…