Abstract:
RATIONALE:Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. OBJECTIVES:Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. METHODS:Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. RESULTS:Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3-quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5-HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin-A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5-HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB-284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. CONCLUSIONS:This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Duxon MS,Stretton J,Starr K,Jones DN,Holland V,Riley G,Jerman J,Brough S,Smart D,Johns A,Chan W,Porter RA,Upton Ndoi
10.1007/s002130000550subject
Has Abstractpub_date
2001-01-01 00:00:00pages
203-9issue
2eissn
0033-3158issn
1432-2072journal_volume
153pub_type
杂志文章abstract:OBJECTIVES:Although cocaine use has been linked to sexual HIV risk behavior for decades, the direct effects of cocaine on sexual desire and sexual decision-making are unexamined. Research suggests delay discounting (devaluation of future outcomes) and probability discounting (devaluation of uncertain outcomes) play rol...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-016-4493-5
更新日期:2017-02-01 00:00:00
abstract:RATIONALE:Buprenorphine reduces both heroin and cocaine intake in opioid addicts, but the mechanisms remain unclear. OBJECTIVES:To determine the effects of chronic buprenorphine treatment on intake of heroin and/or cocaine and measure nucleus accumbens (NAc) dopamine (DA) levels during self-administration. METHODS:In...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0485-1
更新日期:2006-09-01 00:00:00
abstract::The differential sensitivity of young and elderly healthy adults to the impairment effects of benzodiazepines was assessed by tasks with several levels of difficulty. Using a double-blind procedure, single doses of placebo, alprazolam (0.75 and 1.5 mg) and triazolam (0.25 and 0.5 mg) were ingested orally by 10 young m...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02245796
更新日期:1990-01-01 00:00:00
abstract::Rats were presented with noise bursts alone or noise bursts 60 ms after presentation of either a 60 dB or an 80 dB prepulse after injection of the dopamine agonists apomorphine (3 mg/kg) or d-amphetamine (4 mg/kg), the glycine antagonist strychnine (1.5 mg/kg) or the alpha 2 antagonist yohimbine (5 mg/kg). Presentatio...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00174500
更新日期:1988-01-01 00:00:00
abstract::Passive avoidance learning was significantly impaired by atropine (5 mg/kg, IP) or scopolamine (0.5 mg/kg), but not by methyl-atropine (5 mg/kg) or methyl-scopolamine (0.5 mg/kg), from postnatal day 15 on. In contrast, an improvement was observed, not significant at 11 days and significant at 13 days, probably due to ...
journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
abstract:RATIONALE:Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. OBJECTIVES:This study represents a syst...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1827-6
更新日期:2010-06-01 00:00:00
abstract:RATIONALE:The α7 nicotinic acetylcholine receptor (nAChR) has been implicated as a target in modulating nicotine reward. However, the effect of pharmacological agents that have been shown to alter the channel properties of the α7 nAChR is not well understood in nicotine reward. OBJECTIVES:This study aimed to investiga...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-019-05331-y
更新日期:2019-12-01 00:00:00
abstract:RATIONALE:A glutamate-dopamine interaction has been implicated in the psychosis-like effects of glutamate N-methyl- D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine. However, recent imaging studies addressing striatal glutamate-dopamine interaction directly in vivo in man have been controvers...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1236-6
更新日期:2002-12-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02249343
更新日期:1994-04-01 00:00:00
abstract:RATIONALE:The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of b...
journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:2017-08-01 00:00:00
abstract::The effects of bromocriptine, lisuride and apomorphine on specific binding of 3H-spiroperidol to homogenates of rat caudate nucleus were studied. (+)-Butaclamol was used to define specific binding. Bromocriptine and lisuride inhibited binding markedly, in vitro and also 30 min after in vivo injection. Bromocriptine co...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432172
更新日期:1981-01-01 00:00:00
abstract:RATIONALE:The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals. OBJECTIVE:The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied. MATE...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0639-1
更新日期:2007-03-01 00:00:00
abstract::Adult female offspring of C57BL/6J mice injected daily with phenobarbital for the last third of pregnancy were more active than control offspring during a 3-min test period in an open field arena, thus confirming previous reports of lasting effects of prenatal exposure to phenobarbital. These offspring habituated less...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432745
更新日期:1981-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050249
更新日期:1997-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00213-004-1918-3
更新日期:2004-12-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426726
更新日期:1979-03-22 00:00:00
abstract:OBJECTIVES:Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely c...
journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:2013-02-01 00:00:00
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更新日期:2002-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0557-2
更新日期:2006-12-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432855
更新日期:1978-04-11 00:00:00
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更新日期:2012-10-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-009-1585-5
更新日期:2009-09-01 00:00:00
abstract::5-Hydroxytryptamine1A (5-HT1A) receptors have been shown to be suppressed by corticosteroid hormones in a variety of animal experimental paradigms. It has been suggested that this effect may be central to the pathophysiology of severe clinical depressive illness, a condition in which 5-HT1A receptor function is reduce...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002130050711
更新日期:1998-10-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:Functional (pharmacodynamic) ethanol tolerance can be evidenced within a single session of exposure to ethanol (acute or within-session tolerance), or after repeated ethanol exposures (chronic or between-session tolerance). To investigate whether acute and chronic tolerance to ethanol are inter...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100722
更新日期:2001-06-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00213-003-1532-9
更新日期:2003-11-01 00:00:00
abstract::When tested in adulthood, male rats that had been treated daily with 50 mg/kg hydroxyzine HCl SC at 10--29 or 23--29 days of age were significantly facilitated in performance of delayed spontaneous alternation relative to saline-injected rats. Treatment at 10--16 days of age did not produce significant facilitation in...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427646
更新日期:1980-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00172881
更新日期:1986-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00177566
更新日期:1988-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1977-07-18 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00