Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of absence epilepsy.


BACKGROUND AND PURPOSE:Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. EXPERIMENTAL APPROACH:We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. KEY RESULTS:ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg · kg(-1) day(-1)) and risperidone (0.5 mg · kg(-1) day(-1)) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg · kg(-1) day(-1)) and duloxetine (10-30 mg · kg(-1) day(-1)) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg · kg(-1) day(-1) reduced immobility time while at 10 mg · kg(-1) day(-1) an increase was observed. CONCLUSIONS AND IMPLICATIONS:In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour.


Br J Pharmacol


Citraro R,Leo A,De Fazio P,De Sarro G,Russo E




Has Abstract


2015-06-01 00:00:00












  • The extracellular matrix as a key regulator of intracellular signalling networks.

    abstract::The extracellular matrix (ECM) is a salient feature of all solid tissues within the body. This complex, acellular entity is composed of hundreds of individual molecules whose assembly, architecture and biomechanical properties are critical to controlling the behaviour and phenotype of the different cell types residing...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Hastings JF,Skhinas JN,Fey D,Croucher DR,Cox TR

    更新日期:2019-01-01 00:00:00

  • Effect of cyclosporin A and its vehicle on cardiac and skeletal muscle mitochondria: relationship to efficacy of the respiratory chain.

    abstract::Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Sanchez H,Zoll J,Bigard X,Veksler V,Mettauer B,Lampert E,Lonsdorfer J,Ventura-Clapier R

    更新日期:2001-07-01 00:00:00

  • Protease-activated receptor 1 inhibition protects mice against thrombin-dependent respiratory syncytial virus and human metapneumovirus infections.

    abstract:BACKGROUND AND PURPOSE:Protease-activated receptor 1 (PAR1) has been demonstrated to be involved in the pathogenesis of viral diseases. However, its role remains controversial. The goal of our study was to investigate the contribution of PAR1 to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infecti...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lê VB,Riteau B,Alessi MC,Couture C,Jandrot-Perrus M,Rhéaume C,Hamelin MÈ,Boivin G

    更新日期:2018-01-01 00:00:00

  • Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries.

    abstract::Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: de Aguilera EM,Irurzun A,Vila JM,Aldasoro M,Galeote MS,Lluch S

    更新日期:1990-03-01 00:00:00

  • Dual modulation by thrombin of the motility of rat oesophageal muscularis mucosae via two distinct protease-activated receptors (PARs): a novel role for PAR-4 as opposed to PAR-1.

    abstract::Since protease-activated receptors (PARs) are distributed throughout the gastrointestinal tract, we investigated the role of PARs in modulation of the motility of the rat oesophageal muscularis mucosae. Thrombin produced contraction of segments of the upper and lower part of the smooth muscle. Trypsin contracted both ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Kawabata A,Kuroda R,Kuroki N,Nishikawa H,Kawai K

    更新日期:2000-10-01 00:00:00

  • Some pharmacological properties of a synthetic oxytocin analogue [1-N-carbamoyl-hemicystine-2-O-methyltyrosine]-oxytocin (carbamoyl-methyloxytocin), an antagonist to the neurohypophysial hormones.

    abstract::1. A synthetic oxytocin analogue, [1-N-carbamoyl-hemicystine-2-O-methyltyrosine]-oxytocin (carbamoyl-methyloxytocin), has been tested as an antagonist to the actions of oxytocin and vasopressin on the uterus, the mammary gland and blood pressure.2. The analogue inhibited the response of the isolated rat uterus to both...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Bisset GW,Clark BJ,Krejcí I,Polácek I,Rudinger J

    更新日期:1970-10-01 00:00:00

  • Effects of Na+ and K+ on the uptake of metaraminol by rabbit ventricular slices.

    abstract::1. The ionic dependence of [(3)H]-metaraminol transport by rabbit ventricular slices was studied.2. Transport was Na(+) dependent. Choline, Li(+), K(+), Rb(+) or Cs(+) could not be substituted for Na(+).3. Transport was K(+) dependent. Rb(+) and Cs(+), but not Li, could be substituted for K(+), their relative potencie...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Paton DM

    更新日期:1971-01-01 00:00:00

  • Influence of dopamine as noradrenaline precursor on the secretory function of the bovine corpus luteum in vitro.

    abstract::1. Dopamine is assumed to affect the ovary function after its conversion into noradrenaline (NA). 2. To study this bovine luteal slices from 11-14 days of the oestrous cycle were preincubated for 24 h to recover beta-receptors and next they were incubated for 1, 2 or 4 h with (a) different doses of dopamine; (b) dopam...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Kotwica J,Skarzynski D,Bogacki M,Miszkiel G

    更新日期:1996-08-01 00:00:00

  • Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo.

    abstract::1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Laight DW,Kengatharan KM,Gopaul NK,Anggård EE,Carrier MJ

    更新日期:1998-10-01 00:00:00

  • Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid.

    abstract::1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clam...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Kraft R,Grimm C,Frenzel H,Harteneck C

    更新日期:2006-06-01 00:00:00

  • Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen.

    abstract::1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter ove...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Celuch SM,Dubocovich ML,Lander SZ

    更新日期:1978-05-01 00:00:00

  • Melanocortins protect against multiple organ dysfunction syndrome in mice.

    abstract:BACKGROUND AND PURPOSE:Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple or...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Bitto A,Polito F,Altavilla D,Irrera N,Giuliani D,Ottani A,Minutoli L,Spaccapelo L,Galantucci M,Lodi R,Guzzo G,Guarini S,Squadrito F

    更新日期:2011-02-01 00:00:00

  • The stimulation of capsaicin-sensitive neurones in a vanilloid receptor-mediated fashion by pungent terpenoids possessing an unsaturated 1,4-dialdehyde moiety.

    abstract::1. The irritant fungal terpenoid isovelleral caused protective eye-wiping movements in the rat upon intraocular instillation and showed cross-tachyphylaxis with capsaicin, the pungent principle in hot pepper. 2. Isovelleral induced a dose-dependent calcium uptake by rat dorsal root ganglion neurones cultured in vitro ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Szallasi A,Jonassohn M,Acs G,Bíró T,Acs P,Blumberg PM,Sterner O

    更新日期:1996-09-01 00:00:00

  • On the role of 5-hydroxytryptamine in drug-induced antinociception.

    abstract::1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brai...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Sugrue MF

    更新日期:1979-04-01 00:00:00

  • Action of botulinum toxin on transmission from sympathetic nerves to the vas deferens.

    abstract::Botulinum toxin (Type A) depressed or abolished transmission from postganglionic nerves to smooth muscle of isolated preparations of guinea-pig and mouse vas deferens. The time course of blockade was 2 to 6 times slower than that observed with the same concentration of the same batch of toxin on the rat diaphragm. Spo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Holman ME,Spitzer NC

    更新日期:1973-02-01 00:00:00

  • Requirement for endothelium-derived nitric oxide in vasodilation produced by stimulation of cholinergic nerves in rat hindquarters.

    abstract::1. We aimed to determine whether nitric oxide (NO) and/or the endothelium is involved in cholinergic neurogenic vasodilatation in the rat isolated hindquarters. 2. The abdominal aorta was cannulated for perfusion of the rat hindquarters with Krebs bicarbonate solution containing phenylephrine, to induce basal constric...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Loke KE,Sobey CG,Dusting GJ,Woodman OL

    更新日期:1994-06-01 00:00:00

  • Dexmedetomidine and ST-91 analgesia in the formalin model is mediated by alpha2A-adrenoceptors: a mechanism of action distinct from morphine.

    abstract:BACKGROUND AND PURPOSE:Intrathecal administration of alpha(2)-adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal alpha(2)-adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST-91 in the formalin behavioural model and their effects on primary afferent ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Nazarian A,Christianson CA,Hua XY,Yaksh TL

    更新日期:2008-12-01 00:00:00

  • Pharmacology of the octopamine receptor from locust central nervous tissue (OAR3).

    abstract::1. The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure-activity relationships. 2. The high...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Roeder T

    更新日期:1995-01-01 00:00:00

  • Mediation of most atypical effects by species homologues of the beta 3-adrenoceptor.

    abstract::1. A wide panel of compounds acting on beta-adrenoceptors active either in mammalian heart or in rodent digestive tract and adipose tissues, were investigated for their effects on Chinese hamster ovary cells transfected with the human or murine beta 3-adrenoceptor gene. 2. The beta 3-agonists, bucindolol, CGP 12177A a...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Blin N,Nahmias C,Drumare MF,Strosberg AD

    更新日期:1994-07-01 00:00:00

  • Gastric mucosal damage induced by local intra-arterial administration of Paf in the rat.

    abstract::1. A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet-activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3....

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Esplugues JV,Whittle BJ

    更新日期:1988-01-01 00:00:00

  • Wheel running during chronic nicotine exposure is protective against mecamylamine-precipitated withdrawal and up-regulates hippocampal α7 nACh receptors in mice.

    abstract:BACKGROUND AND PURPOSE:Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 n...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Keyworth H,Georgiou P,Zanos P,Rueda AV,Chen Y,Kitchen I,Camarini R,Cropley M,Bailey A

    更新日期:2018-06-01 00:00:00

  • A pharmacological analysis of receptors mediating the excitatory response to 5-hydroxytryptamine in the guinea-pig isolated trachea.

    abstract::1. Experiments were carried out to characterize the receptors mediating the indirect excitatory response to 5-hydroxytryptamine (5-HT) in the guinea-pig isolated trachea. 2. 5-HT caused concentration-dependent contractions of tracheal strips, and the resulting concentration-response curve was biphasic in nature. The f...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lucchelli A,Santagostino-Barbone MG,Barbieri A,Tonini M

    更新日期:1994-07-01 00:00:00

  • Involvement of nitric oxide in the inhibition of angiogenesis by interleukin-2.

    abstract::Interleukin-2 (IL-2), an immunoregulatory cytokine possessing antitumour activity, is an inducer of nitric oxide (NO) synthesis in mice and man. In this study, the possibility that IL-2 possesses antiangiogenic properties that account for its antitumour effects in vivo was examined. IL-2 caused a dose-dependent inhibi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Sakkoula E,Pipili-Synetos E,Maragoudakis ME

    更新日期:1997-11-01 00:00:00

  • Targeted inhibition of IL-18 attenuates irinotecan-induced intestinal mucositis in mice.

    abstract:BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lima-Júnior RC,Freitas HC,Wong DV,Wanderley CW,Nunes LG,Leite LL,Miranda SP,Souza MH,Brito GA,Magalhães PJ,Teixeira MM,Cunha FQ,Ribeiro RA

    更新日期:2014-05-01 00:00:00

  • Salmeterol-induced desensitization, internalization and phosphorylation of the human beta2-adrenoceptor.

    abstract::1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the abil...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: January B,Seibold A,Allal C,Whaley BS,Knoll BJ,Moore RH,Dickey BF,Barber R,Clark RB

    更新日期:1998-02-01 00:00:00

  • Investigation of the prostaglandin E (EP-) receptor subtype mediating relaxation of the rabbit jugular vein.

    abstract::1. Prostaglandin E2 (PGE2) relaxes circular smooth muscle of the rabbit isolated jugular vein at very low concentrations (mean pIC50 against histamine-induced contraction = 9.34). This effect is not blocked by the EP1-receptor antagonist, AH 6809 (2 microM). 2. From a group of prostaglandin E analogues examined, 16,16...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lawrence RA,Jones RL

    更新日期:1992-04-01 00:00:00

  • Noradrenaline-induced relaxation of rat oesophageal muscularis mucosae: mediation solely by innervated beta 3-adrenoceptors.

    abstract::We investigated the effects of cocaine and corticosterone on the noradrenaline-induced relaxation of rat oesophageal smooth muscle in the absence and presence of the selective beta2-antagonist, ICI 111,551. It was found that the concentration-response curve (CRC) of noradrenaline was not shifted by ICI 118,551 at 1 mi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: de Boer RE,Brouwer F,Zaagsma J

    更新日期:1995-10-01 00:00:00

  • Quinoxalinediones selectively block quisqualate and kainate receptors and synaptic events in rat neocortex and hippocampus and frog spinal cord in vitro.

    abstract::1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate w...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Fletcher EJ,Martin D,Aram JA,Lodge D,Honoré T

    更新日期:1988-10-01 00:00:00

  • Inhibitory effect of sodium cromoglycate on pulmonary responses to histamine administered after indomethacin in anaesthetized guinea-pigs.

    abstract::1. Histamine (2-4 micrograms kg-1 i.v.) increased airways resistance (Raw) and decreased dynamic lung compliance (Cdyn) in urethane-anaesthetized guinea-pigs. The effects on Raw were almost abolished by atropine (0.1 mg kg-1 i.v.) and reduced by vagal cooling (11-16 degrees C). 2. Histamine-induced changes in Raw and ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Mitchell HW

    更新日期:1988-06-01 00:00:00

  • Effects of verapamil on the response of the guinea-pig tracheal muscle to carbachol.

    abstract::The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2+) or barium (Ba2+) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contrac...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Baba K,Satake T,Takagi K,Tomita T

    更新日期:1986-06-01 00:00:00