Abstract：
BACKGROUND AND PURPOSE:Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD-related markers. EXPERIMENTAL APPROACH:Anhedonia induced by a chronic mild stress (CMS) procedure, applied for 6 weeks, was used to select rats vulnerable or resistant to stress. Sucrose intake, the Porsolt forced swimming test and cognitive deficits in the novel object recognition test (NORT) were used to characterize vulnerable and resilient rats. The antidepressant venlafaxine (20 mg·kg(-1) p.o.) or saline was administered daily during the last 2 weeks of CMS. Biochemical markers affected by stress, PKB, ERK and synaptophysin, and those associated with AD, amyloid β-protein (Aβ), β-secretase (BACE1) and τ phosphorylation, were measured in the hippocampus. KEY RESULTS:After CMS, 40% of rats were resistant to the development of anhedonia (CMS-resistant to stress), whereas the remaining were responsive [CMS-anhedonic (CMSA)]. Only CMSA rats displayed significant increases in immobility time in the forced swimming test and cognitive deficits in the NORT, and significant decreases in synaptophysin, phosphorylated PKB and phosphorylated ERK1/2 expression in the hippocampus. Increased levels of Aβ40, BACE1 and τ phosphorylation were also found only in CMSA rats. All these effects in CMSA rats were reverted by treatment with venlafaxine. CONCLUSIONS AND IMPLICATIONS:Vulnerability to stress might constitute a risk factor for the development of AD, and pharmacological treatment with venlafaxine may represent a therapeutic strategy for the treatment of stress-related disorders, including AD.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Briones A,Gagno S,Martisova E,Dobarro M,Aisa B,Solas M,Tordera R,Ramírez Mdoi
10.1111/j.1476-5381.2011.01602.xsubject
Has Abstractpub_date
2012-02-01 00:00:00pages
897-907issue
4eissn
0007-1188issn
1476-5381journal_volume
165pub_type
杂志文章abstract：:The non-peptide NK1 receptor antagonist, CP-96,345, and its 2R,3R enantiomer CP-96,344, which is not an NK1 receptor antagonist (IC50 > 10 microM), were evaluated for antinociceptive and anti-inflammatory activities in several classical models of pain and inflammation in the rat. Both CP-96,345 and CP-96,344 reduced c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12737.x
更新日期：1992-10-01 00:00:00
abstract：:1 Tissue was taken from guinea-pigs that had been injected with guanethidine (100 mg/kg, i.p.) 24 h before they were killed, and from paired control animals.2 Pretreatment with guanethidine caused a significant, substantial, and sometimes complete reduction of the nerve-mediated contractions of the vas deferens. There...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09593.x
更新日期：1974-01-01 00:00:00
abstract：:1. Two-electrode voltage clamp was used to study the effects of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP) on voltage-dependent ion channels in salivary gland cells of the leech, Haementeria ghilianii. 2. Intracellular cyclic AMP specifically blocked delayed...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16673.x
更新日期：1995-09-01 00:00:00
abstract：:1. The effects of (-)-isoprenaline and the new beta-adrenoceptor agonist, MJ-9184-1, on the lungs, on the cardiovascular system, and on slow contracting skeletal muscle have been compared in cats under chloralose anaesthesia.2. Both amines reduced the increases in airways resistance produced by 5-HT, depressed incompl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08134.x
更新日期：1972-11-01 00:00:00
abstract：:1. The interactions between N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors (mGluRs) were investigated in striatal slices, by utilizing intracellular recordings, both in current- and voltage-clamp mode. 2. Bath-application (50 microM) or focal application of NMDA induced a transient membrane depolariz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700999
更新日期：1997-03-01 00:00:00
abstract：:1. The agonist action of the opioid peptide dynorphin A(1-8) on the myenteric plexus-longitudinal muscle of the guinea-pig ileum has been characterized. 2. The endogenous opioid peptide dynorphin A(1-8) was rapidly degraded by slices of myenteric plexus-longitudinal muscle of the guinea-pig ileum. 3. A product of the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14139.x
更新日期：1990-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01379.x
更新日期：2011-08-01 00:00:00
abstract：:Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused o...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01711.x
更新日期：2012-04-01 00:00:00
abstract：:There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705480
更新日期：2003-10-01 00:00:00
abstract：:We have examined the effects of antagonists on the isometric contraction of the human saphenous vein produced by 5-hydroxytryptamine (5-HT). The 5-HT2-antagonist ketanserin (1 microM) had little effect on the lower part of the concentration-response curve to 5-HT, but markedly shifted the upper part of the curve. Yohi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11122.x
更新日期：1986-09-01 00:00:00
abstract：:1. Previous studies demonstrated that elevation of the extracellular calcium concentration during a prolonged exposure to a high concentration of carbachol reverses the staurosporine-induced decrease in the extent of endplate resensitization in voltage-clamped snake twitch fibres. The present studies were designed to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13896.x
更新日期：1993-10-01 00:00:00
abstract：:The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 micro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703754
更新日期：2000-12-01 00:00:00
abstract：:1. The role of vasoconstrictor 5-HT1-like receptors in the control of vascular reactivity in vivo has been relatively little studied, particularly with regards to venous function. Using an anaesthetized dog model, we have investigated the haemodynamic profile of the selective 5-HT1-like agonist, sumatriptan, focussing...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15055.x
更新日期：1995-10-01 00:00:00
abstract：:Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707657
更新日期：2008-04-01 00:00:00
abstract：:1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700885
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of vari...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00493.x
更新日期：2009-12-01 00:00:00
abstract：:1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-depen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14708.x
更新日期：1990-02-01 00:00:00
abstract：:1. The purpose of the present study was to identify and investigate the role of 5-hydroxytryptamine3 (5-HT3) receptors in the area postrema in the control of cisplatin-induced emesis in the ferret. 2. Homogenate binding and autoradiography experiments using the high affinity 5-HT3 receptor ligand, [3H]-GR65630, identi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11948.x
更新日期：1989-05-01 00:00:00
abstract：:1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-met...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11813.x
更新日期：1989-02-01 00:00:00
abstract：:1. Turning behaviour after unilateral lesions of the nigro-striatal dopamine pathway in rats has been used to compare the actions of cocaine and desipramine on central dopamine-containing neurones.2. Administration of cocaine alone (5-20 mg/kg) resulted in no turning or minimal turning towards the lesioned side; the m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08156.x
更新日期：1973-01-01 00:00:00
abstract：:1. In rat aortic rings contracted by phenylephrine, the relaxation induced by isoprenaline was partly inhibited by iberiotoxin, (ibTX), tetraethylammonium, 4-aminopyridine (4-AP) and 1,9-dideoxyforskolin, but not by glibenclamide. 2. In the presence of 4-AP, 1,9-dideoxyforskolin failed to inhibit further the relaxant ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15700.x
更新日期：1996-10-01 00:00:00
abstract：:1. We investigated the role of two conserved basic residues in the second transmembrane helix arginine 172 (R172) and lysine 179 (K179) of the VPAC(2) receptor. 2. Vasoactive intestinal polypeptide (VIP) activated VPAC(2) receptors with an EC(50) value of 7 nM, as compared to 150, 190 and 4000 nM at R172L, R172Q and K...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704195
更新日期：2001-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Orexins have been demonstrated to play important roles in many physiological processes. However, it is not known how orexin A affects the activity of the hypoglossal motoneuron (HMN) and genioglossus (GG) muscle. EXPERIMENTAL APPROACH:GG muscle electromyograms (GG-EMG) were recorded in anaesthet...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12784
更新日期：2014-09-01 00:00:00
abstract：:Specific [125I]-angiotensin II (AII) and [125I]-bradykinin (Bk) binding sites have been identified within epithelial membranes from rat jejunum and descending colon. These high affinity intestinal sites exhibited KD values of 0.64 +/- 0.16 nM for [125I]-AII and 0.69 +/- 0.13 nM for [125I]-Bk, which were similar to tho...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10172.x
更新日期：1986-01-01 00:00:00
abstract：:1. The effects of the intravenous injection of Kö 1173, a new anticonvulsant drug, phenytoin and procainamide were studied on three types of cardiac arrhythmia in dogs.2. Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished by Kö 1173, 0...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08114.x
更新日期：1972-08-01 00:00:00
abstract：:We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706311
更新日期：2005-09-01 00:00:00
abstract：:An increasing number of examples in the literature suggest that the in vivo duration of drug action not only depends on macroscopic pharmacokinetic properties like plasma half-life and the time needed to equilibrate between the plasma and the effect compartments, but is also influenced by long-lasting target binding a...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2010.00936.x
更新日期：2010-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13124
更新日期：2015-07-01 00:00:00
abstract：:1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of single neurones to iontophoretically applied excitatory amino acids. The tests were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized rat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13156.x
更新日期：1994-07-01 00:00:00
abstract：:1. Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, live...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703826
更新日期：2001-01-01 00:00:00
