The orexin system regulates alcohol-seeking in rats.


:1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of alcohol-seeking behaviour, and also attenuated alcohol responding under an operant fixed ratio regimen without affecting water responding. 3. The mRNA encoding orexin within the hypothalamus was expressed at a similar density in iP and non-preferring (NP) rats; chronic consumption of ethanol in iP rats did not significantly regulate the density of this expression, but did increase the area of expression within the lateral, but not medial, hypothalamus. 4. These data indicate that while orexin may not be implicated in the development of an alcohol preference, re-exposure of cues previously associated with alcohol availability is sufficient and adequate to activate orexin-containing neurons and drive reinstatement of alcohol-seeking.


Br J Pharmacol


Lawrence AJ,Cowen MS,Yang HJ,Chen F,Oldfield B




Has Abstract


2006-07-01 00:00:00














  • Use of knockout technology to resolve pharmacological problems.

    abstract::Knock-out (KO) mouse technology has given pharmacologists a powerful tool to study function in the absence of selective antagonists or inhibitors. Such KO technology can confirm predicted function, serendipitously reveal unrecognized function, or help define the mode of action of a drug. In this issue, Liles et al. de...

    journal_title:British journal of pharmacology

    pub_type: 评论,杂志文章


    authors: Docherty JR

    更新日期:2007-01-01 00:00:00

  • Evaluation of ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, with a PGD2-responsive cell line from bovine embryonic trachea.

    abstract::ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ito S,Okuda E,Sugama K,Negishi M,Hayaishi O

    更新日期:1990-01-01 00:00:00

  • Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.

    abstract:BACKGROUND AND PURPOSE:We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms sup...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Barrière DA,Boumezbeur F,Dalmann R,Cadeddu R,Richard D,Pinguet J,Daulhac L,Sarret P,Whittingstall K,Keller M,Mériaux S,Eschalier A,Mallet C

    更新日期:2020-04-01 00:00:00

  • Assessment of selective beta-adrenoceptor blockade in man.

    abstract::1. Selective antagonism of the cardiac beta(1)-adrenoceptors has been studied in normal human volunteers.2. Practolol and UK 6558 produced greater antagonism of the chronotropic and inotropic responses to i.v. isoprenaline than of the vasodilator response to either i.v. or intra-arterial isoprenaline. A third drug, M&...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Briant RH,Dollery CT,Fenyvesi T,George CF

    更新日期:1973-09-01 00:00:00

  • Pharmacokinetic interaction between DA-8159, a new erectogenic, and metformin in rats: competitive inhibition of metabolism via hepatic CYP3A1/2.

    abstract:BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Choi YH,Chung SJ,Lee MG

    更新日期:2008-04-01 00:00:00

  • Drug displacement from protein binding: isolation of a redistributional drug interaction in vivo.

    abstract::1. The pharmacokinetic interaction between phenylbutazone and sulphadoxine has been studied in live sheep.2. Intravenous injection of phenylbutazone causes a rapid fall in the concentration of total sulphadoxine together with a simultaneous rise in the concentration of free sulphadoxine in plasma. Both processes are c...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: McQueen EG,Wardell WM

    更新日期:1971-10-01 00:00:00

  • Relationships between chemical structure and affinity for acetylcholine receptors.

    abstract::1. Series of analogues of acetylcholine have been prepared in which the acetyl group was replaced by phenylacetyl, cyclohexylacetyl, diphenylacetyl, dicyclohexylacetyl, (+/-)-phenylcyclohexylacetyl, benziloyl and (+/-)-phenylcyclohexylhydroxyacetyl groups and the trimethylammonium group was replaced by Me(2)EtN(+), Me...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Abramson FB,Barlow RB,Mustafa MG,Stephenson RP

    更新日期:1969-09-01 00:00:00

  • Time-dependent stimulatory and inhibitory effects of prostaglandin E1 on exudative and tissue components of granulomatous inflammation in rats.

    abstract::1 The effects of prostaglandin (PGE(1)), following local administration during different phases of developing sponge-induced granulomata, were studied in normal and essential fatty acid deficient (EFAD) rats.2 In normal rats, a single dose of 1 mug PGE(1) on implantation (day 1) increased exudate production without al...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Bonta IL,Parnham MJ

    更新日期:1979-03-01 00:00:00

  • Spinal antinociceptive effects of the novel NOP receptor agonist PWT2-nociceptin/orphanin FQ in mice and monkeys.

    abstract:BACKGROUND AND PURPOSE:Using an innovative chemical approach, peptide welding technology (PWT), a tetrabranched derivative of nociceptin/orphanin FQ (N/OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2-N/OFQ displayed the same pharmacological profile to the natural ligand. It w...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Rizzi A,Sukhtankar DD,Ding H,Hayashida K,Ruzza C,Guerrini R,Calò G,Ko MC

    更新日期:2015-07-01 00:00:00

  • Pinacidil opens K+-selective channels causing hyperpolarization and relaxation of noradrenaline contractions in rat mesenteric resistance vessels.

    abstract::1. The effects of pinacidil on noradrenaline-induced tone, smooth muscle membrane potential and 42K- and 86Rb-efflux from isolated mesenteric resistance vessels (internal diameter 200 microns) of the rat have been studied. 2. Pinacidil (0.3-10 microM) produced concentration-dependent suppression of noradrenaline-induc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Videbaek LM,Aalkjaer C,Mulvany MJ

    更新日期:1988-09-01 00:00:00

  • Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.

    abstract::1. Glycine responses were studied under voltage clamp in Xenopus oocytes injected with cDNA encoding mammalian glycine receptor subunits and in rat medullary neurones. Bath application of glycine gave strychnine-sensitive currents which reversed close to the expected equilibrium potentials for chloride ions. The peak ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Downie DL,Hall AC,Lieb WR,Franks NP

    更新日期:1996-06-01 00:00:00

  • Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion.

    abstract::1. The polymorphonuclear neutrophils (PMN) activation and mobilization observed in acute cerebral infarction contribute to the brain tissue damage, but PMN could also be involved in postischemic functional injury of ischemied blood vessel. 2. This study was undertaken to investigate whether pharmacological neutropenia...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Pétrault O,Ouk T,Gautier S,Laprais M,Gelé P,Bastide M,Bordet R

    更新日期:2005-04-01 00:00:00

  • Isothiouronium compounds as gamma-aminobutyric acid agonists.

    abstract::Analogues of gamma-aminobutyric acid (GABA) incorporating an isothiouronium salt as a replacement for a protonated amino functional group have been investigated for activity on: GABA receptors in the guinea-pig ileum; [3H]-GABA and [3H]-diazepam binding to rat brain membranes; and GABA uptake and transamination. For t...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Allan RD,Dickenson HW,Hiern BP,Johnston GA,Kazlauskas R

    更新日期:1986-06-01 00:00:00

  • Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension.

    abstract:BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Hernanz R,Martínez-Revelles S,Palacios R,Martín A,Cachofeiro V,Aguado A,García-Redondo L,Barrús MT,de Batista PR,Briones AM,Salaices M,Alonso MJ

    更新日期:2015-06-01 00:00:00

  • Pharmacological mapping of regional effects in the rabbit heart of some new antiarrhythmic drugs.

    abstract::In vitro preparations of rabbit heart were made from which measurements of effective refractory period (ERP), atrio-Hisian (A-H) and His-Purkinje (H-P) conduction times could be obtained, analogous to electrophysiological measurements customarily carried out in vivo. Intracellular potentials also were recorded from th...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Millar JS,Vaughan Williams EM

    更新日期:1983-07-01 00:00:00

  • Endothelium-independent relaxation of rabbit coronary artery by 17 beta-oestradiol in vitro.

    abstract::1. We assessed the relaxant effect of 17 beta-oestradiol (10(-7), 10(-6) and 10(-5) M) on rabbit isolated coronary arteries precontracted with prostaglandin F2 alpha (3 x 10(-6) M), high extracellular potassium (30 mM) and Bay K 8644 (10(-6) M) plus high extracellular potassium (15 mM) by measuring isometric tension. ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Jiang CW,Sarrel PM,Lindsay DC,Poole-Wilson PA,Collins P

    更新日期:1991-12-01 00:00:00

  • Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase.

    abstract::The effect of activation of protein kinase C (PKC) or adenylyl cyclase on release of glutamate has been investigated in a perfused slice preparation from the rat caudal trigeminal nucleus. Stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) produced a concentration-dependent increase in K(+)-evoked release of ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Maneuf YP,McKnight AT

    更新日期:2001-09-01 00:00:00

  • [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray.

    abstract::1. [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 (Phepsi), a tridecapeptide analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competitive antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig ileum and mouse vas deferens preparations in vitro but was recently found to act as an agonist i...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Chiou LC

    更新日期:1999-09-01 00:00:00

  • Identification of novel insulin mimetic drugs by quantitative total internal reflection fluorescence (TIRF) microscopy.

    abstract:BACKGROUND AND PURPOSE:Insulin stimulates the transport of glucose in target tissues by triggering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Resistance to insulin, the major abnormality in type 2 diabetes, results in a decreased GLUT4 translocation efficiency. Thus, special attention is...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lanzerstorfer P,Stadlbauer V,Chtcheglova LA,Haselgrübler R,Borgmann D,Wruss J,Hinterdorfer P,Schröder K,Winkler SM,Höglinger O,Weghuber J

    更新日期:2014-12-01 00:00:00

  • Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin.

    abstract:BACKGROUND AND PURPOSE:Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Medina C,Harmon S,Inkielewicz I,Santos-Martinez MJ,Jones M,Cantwell P,Bazou D,Ledwidge M,Radomski MW,Gilmer JF

    更新日期:2012-06-01 00:00:00

  • The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions.

    abstract::1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Barr RM,Koro O,Francis DM,Black AK,Numata T,Greaves MW

    更新日期:1988-07-01 00:00:00

  • The actions of dehydroemetine on isolated guinea-pig atria. Influence of ouabain and calcium.

    abstract::1. The mechanism of the inhibitory effect of dehydroemetine on the heart was investigated using (a) the spontaneously contracting isolated guinea-pig atrial preparation and (b), the electrically driven left atrial preparation.2. Dehydroemetine decreased the rate and amplitude of contraction of spontaneously contractin...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Salako LA

    更新日期:1972-12-01 00:00:00

  • Synthesis of new haloperidol analogues and characterization of their interactions with alpha-adrenoceptors in rat parotid slices and human platelet membranes.

    abstract::1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adreno...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Atlas D,Friedman Z,Litvin Y,Steer ML

    更新日期:1982-01-01 00:00:00

  • Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism.

    abstract:BACKGROUND AND PURPOSE:Although CB(1) receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of can...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Sun Y,Alexander SP,Garle MJ,Gibson CL,Hewitt K,Murphy SP,Kendall DA,Bennett AJ

    更新日期:2007-11-01 00:00:00

  • Characterization of the functional muscarinic receptors in the rat urinary bladder.

    abstract::1. Muscarinic receptors mediating contraction of the rat urinary bladder were characterized functionally in vitro by use of atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP methiodide), 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (4-DAMP mustard), hexahydro-sila-diphenidol hydrochlori...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Longhurst PA,Leggett RE,Briscoe JA

    更新日期:1995-10-01 00:00:00

  • Inter-study variability of preclinical in vivo safety studies and translational exposure-QTc relationships--a PKPD meta-analysis.

    abstract:BACKGROUND AND PURPOSE:Preclinical cardiovascular safety studies (CVS) have been compared between facilities with respect to their sensitivity to detect drug-induced QTc prolongation (ΔQTc). Little is known about the consistency of quantitative ΔQTc predictions that are relevant for translation to humans. EXPERIMENTAL...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,meta分析


    authors: Gotta V,Cools F,van Ammel K,Gallacher DJ,Visser SA,Sannajust F,Morissette P,Danhof M,van der Graaf PH

    更新日期:2015-09-01 00:00:00

  • Dualistic actions of cromakalim and new potent 2H-1,4-benzoxazine derivatives on the native skeletal muscle K ATP channel.

    abstract::1 New 2H-1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K(+) channels (K(ATP)) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituent...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Tricarico D,Barbieri M,Antonio L,Tortorella P,Loiodice F,Camerino DC

    更新日期:2003-05-01 00:00:00

  • Some effects of PCO2 and pH on nerve tissue.

    abstract::1. Rat phrenic nerve preparations were used in vitro to study action potential amplitude and nerve conduction time under varying conditions of Pco(2) and sodium bicarbonate concentration in the surrounding Krebs solution.2. A correlation was found between action potential amplitude and pH but not between action potent...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ellis FR

    更新日期:1969-01-01 00:00:00

  • Effect of etorphine, morphine and diprenorphine on neurones of the cerebral cortex and spinal cord of the rat.

    abstract::1. The actions of etorphine, morphine and diprenorphine were investigated on neurones of the cerebral cortex and spinal cord of rats anaesthetized with pentobarbitone.2. In the cerebral cortex, intravenous etorphine increased the latency of the primary evoked response to a peripheral nerve stimulus and suppressed the ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Biscoe TJ,Duggan AW,Lodge D

    更新日期:1972-10-01 00:00:00

  • Comparison of autonomic responses in the trachea isolated from normal and albumin-sensitive guinea-pigs.

    abstract::1 Mechanical and electrical responses to stimulation of the parasympathetic and sympathetic nerves were compared in the trachea isolated from normal guinea-pigs and from guinea-pigs sensitized to albumin and exposed repeatedly to inhaled albumin (a model of bronchial asthma). 2 Sensitized trachealis exhibited mechanic...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: McCaig DJ

    更新日期:1987-12-01 00:00:00