Abstract:
RATIONALE:Latent inhibition (LI), namely, poorer performance on a learning task involving a previously pre-exposed non-reinforced stimulus, is disrupted in the rat by the dopamine (DA) releaser amphetamine which produces and exacerbates psychotic (positive) symptoms, and this is reversed by treatment with typical and atypical antipsychotic drugs (APDs) which on their own potentiate LI. These phenomena are paralleled by disrupted LI in normal amphetamine-treated humans, in high schizotypal humans, and in schizophrenia patients in the acute stages of the disorder, as well as by potentiated LI in normal humans treated with APDs. Consequently, disrupted LI is considered to provide an animal model of positive symptoms of schizophrenia with face, construct and predictive validity. OBJECTIVES:To review most of the rodent data on the neural substrates of LI as well as on the effects of APDs on this phenomenon with an attempt to interpret and integrate these data within the framework of the switching model of LI; to show that there are two distinct LI models, disrupted and abnormally persistent LI; to relate these findings to the clinical condition. RESULTS:The nucleus accumbens (NAC) and its DA innervation form a crucial component of the neural circuitry of LI, and are involved at the conditioning stage. There is a clear functional differentiation between the NAC shell and core subregions whereby damage to the shell disrupts LI and damage to the core renders LI abnormally persistent under conditions that disrupt LI in normal rats. The effects of shell and core lesions parallel those produced by lesions to the major sources of input to the NAC: entorhinal cortex lesion, like shell lesion, disrupts LI, whereas hippocampal lesion, like core lesion, produces persistent LI with changes in context, and basolateral amygdala (BLA) lesion, like core lesion, produces persistent LI with extended conditioning. Systemically induced blockade of glutamatergic as well as DA transmission produce persistent LI via effects exerted at the conditioning stage, whereas enhancement of DA transmission disrupts LI via effects at the conditioning stage. Serotonergic manipulations can disrupt or potentiate LI via effects at the pre-exposure stage. Both typical and atypical APDs potentiate LI via effects at conditioning whereas atypical APDs in addition disrupt LI via effects at pre-exposure. Schizophrenia patients can exhibit disrupted or normal LI as a function of the state of the disorder (acute versus chronic), as well as persistent LI. CONCLUSIONS:Different drug and lesion manipulations produce two poles of abnormality in LI, namely, disrupted LI under conditions which lead to LI in normal rats, and abnormally persistent LI under conditions which disrupt it in normal rats. Disrupted and persistent LI are differentially responsive to APDs, with the former reversed by both typical and atypical APDs and the latter selectively reversed by atypical APDs. It is suggested that this "two-headed LI model" mimics two extremes of deficient cognitive switching seen in schizophrenia, excessive and retarded switching between associations, mediated by dysfunction of different brain circuitries, and can serve to model positive symptoms of schizophrenia and typical antipsychotic action, as well as negative symptoms of schizophrenia and atypical antipsychotic action.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Weiner Idoi
10.1007/s00213-002-1313-xsubject
Has Abstractpub_date
2003-09-01 00:00:00pages
257-97issue
3-4eissn
0033-3158issn
1432-2072journal_volume
169pub_type
杂志文章,评审abstract::The effects of eight serotonin (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine (3.0 mg/kg, IP) were examined in a test of sweet mash consumption, using non-deprived male rats. d-Fenfluramine's effect was attenuated by the mixed 5-HT1/5-HT2 receptor antagonists, methiothepin and metergoline; by th...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00442252
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Acute diazepam administration has been shown to decrease plasma cortisol levels consistent with decreased activity of the hypothalamic-pituitary-adrenal axis, especially in individuals experiencing stress. However, the effects of chronic diazepam treatment on cortisol have been less studied, and the relations...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00213-004-1974-8
更新日期:2005-02-01 00:00:00
abstract:RATIONALE:Cocaine addiction is a relapsing psychiatric disorder with a high prevalence in developed countries. To date, the reinstatement model has been difficult to implement in mice. The design of an appropriate reinstatement model in mice is required in order to use genetically modified animals with the aim of clari...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-008-1184-x
更新日期:2008-09-01 00:00:00
abstract::The effects of acutely or chronically administered carbamazepine were studied in rats submitted to the modified Geller-Seifter conflict test. Diazepam was used as a standard anxiolytic. The results showed an increase in punished response after carbamazepine, as observed with diazepam, leading to the suggestion of an a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244411
更新日期:1990-01-01 00:00:00
abstract::In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle, pretreatment with the D1 DA antagonists, SCH 23390 (7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepin e) and A66359 (1- 2-bromo-4,5-dimethoxybenzyl]-7-hydroxy-6-methoxy-2-methyl- 1,2,3,4 tetrahydroisoquinol...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246211
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. OBJECTIVES:The aim of this study was to evaluate the effect of Valeriana officinalis root extract on preventio...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-014-3716-x
更新日期:2015-03-01 00:00:00
abstract::The discriminative stimulus effect of midazolam, a short-acting benzodiazepine, was used for testing the effects of drugs thought to act as antagonists at different sites in the proposed benzodiazepine receptor complex. Rats were trained in a standard two-bar operant conditioning procedure with food reinforcers delive...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00310626
更新日期:1986-01-01 00:00:00
abstract::The urinary excretion of 4-hydroxy-3-methoxyphenylglycol was compared in a group of 23 depressive patients and 27 control subjects of similar age. There was no difference between patients and controls although female controls excreted less than males. After 6 weeks' treatment with 150 mg daily of amitriptyline there w...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427352
更新日期:1979-06-28 00:00:00
abstract::There is little evidence concerning the effects of caffeine in doses typical of one cup of tea. The present study investigated the effect of 60 mg caffeine, consumed in either tea or hot water, on performance on a subset of the CANTAB test battery. Eight males participated in a practice session and four test sessions....
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050746
更新日期:1998-11-01 00:00:00
abstract::Using a 15-s intershock interval, an increase in shock-induced fighting was observed following intraventricular 96 microgram 5,7-dihydroxytryptamine (5,7-DHT) and 90 microgram 6-hydroxydopa (6-OHdopa). The incidence of predatory mouse killing was enhanced by 5,7-DHT, but was not affected by 6-OHdopa. Pain sensitivity ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432684
更新日期:1981-01-01 00:00:00
abstract:RATIONALE:Deficits in response inhibition associated with heroin use could last several months after abstinence in heroin users, and their response inhibition can also be interfered with task-irrelevant drug-related cues. However, it is unclear whether exposure to drug-related cues affects subsequent response inhibitio...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-019-05434-6
更新日期:2020-04-01 00:00:00
abstract:RATIONALE:Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. OBJECTIVE:We investigated the role of α2-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model o...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-016-4416-5
更新日期:2016-10-01 00:00:00
abstract:RATIONALE:Piper methysticum extract (kava kava) possesses numerous therapeutic properties, but it is unknown which of its principle constituents (kavalactones) subserve such effects. OBJECTIVES:This experiment sought to characterize the putative anxiolytic properties of P. methysticum extract and its six principle kav...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100686
更新日期:2001-04-01 00:00:00
abstract::After publication of this paper, the authors determined an error in Fig. 2C. ...
journal_title:Psychopharmacology
pub_type: 已发布勘误
doi:10.1007/s00213-019-05269-1
更新日期:2019-07-01 00:00:00
abstract:RATIONALE:Delta-opioid agonists produce a number of behavioral effects, including convulsions, antinociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-0138-9
更新日期:2005-11-01 00:00:00
abstract:RATIONALE:Alcohol intoxication can dampen negative affective reactions to stressors. Recently, it has been proposed that these acute anxiolytic effects of alcohol may extend to dampening of negative affective reactions to error commission during cognitive control tasks. Nonetheless, empirical verification of this claim...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05619-4
更新日期:2020-11-01 00:00:00
abstract:RATIONALE:Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine depend...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3685-0
更新日期:2015-01-01 00:00:00
abstract:RATIONALE:It has been proposed that cannabinoid-1 receptor inverse agonists might be effective for smoking cessation. We evaluated this hypothesis with the cannabinoid-1 receptor inverse agonist taranabant. METHODS:Adults who smoked > or =10 cigarettes a day for >1 year and had an expired CO level of > or =10 ppm part...
journal_title:Psychopharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00213-010-1790-2
更新日期:2010-04-01 00:00:00
abstract::The effect of aluminum on levels of inorganic phosphorus and acetylcholinesterase in blood and brain and on permeability of the blood-brain barrier (BBB) in different regions of the brain to the neuropeptide delta-sleep-inducing peptide (DSIP) was studied in adult rats. Aluminum (100 mg/kg) significantly increased the...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00431689
更新日期:1985-01-01 00:00:00
abstract::When injected IP, the M1 muscarinic receptor antagonist pirenzepine dose-dependently induced a deficit in passive avoidance learning in rats. This activity was optimal at 75 mg/kg injected 1 h before the acquisition session. The deficit induced by pirenzepine was antagonized by oxotremorine (0.03-0.3 mg/kg SC) and phy...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00444707
更新日期:1989-01-01 00:00:00
abstract:RATIONALE:Research suggests the experimental manipulation of oxytocin facilitates positive interactions, cooperation, and trust. The mechanism by which oxytocin influences social behavior is not well understood. OBJECTIVE:We explored the hypothesis that oxytocin alters how people perceive themselves, which could be on...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2527-6
更新日期:2012-04-01 00:00:00
abstract::In two experiments, phenobarbitone sodium (30 mg/kg) reliably enhanced water consumption and extended the duration of drinking in 24h water-deprived male rats. The opiate receptor antagonists naloxone (0.1-10 mg/kg) and naltrexone (0.1-10 mg/kg) both decreased water intake and reduced the duration of drinking. When th...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433011
更新日期:1983-01-01 00:00:00
abstract::The benzodiazepine diazepam and the benzodiazepine antagonist Ro 15-1788 were tested alone or in combination for their influence on scopolamine-induced locomotor stimulation in mice. The benzodiazepine antagonist had no effect by itself, but prevented the enhancement of scopolamine-induced locomotor stimulation produc...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00464583
更新日期:1982-01-01 00:00:00
abstract:INTRODUCTION:The objective of this study was to examine age-, hormone-, and sex-dependent differences to the behavioral effects of nicotine using place-conditioning procedures in female rats. METHODS:Animals received nicotine in their initially non-preferred side and saline on alternate days in their initially preferr...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-009-1607-3
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Alcohol drinking may lead to increased aggression in certain individuals, and both fighting and drinking increase levels of dopamine and serotonin in mesocorticolimbic structures. Assessing the dynamic changes in these neurotransmitters during the course of drinking and fighting has remained challenging. OB...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0637-3
更新日期:2007-04-01 00:00:00
abstract::Animals responding for biphasic square wave stimulation to the VTA were treated for 26 days with a low dose (0.07 mg/kg) of the neuroleptic haloperidol and tested at 1 h post-injection. Initially the drug induced a pronounced lateral displacement of the baseline rate-intensity function, concomitant with a depression i...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245756
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability. OBJECTIVES:The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abus...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-017-4665-y
更新日期:2017-09-01 00:00:00
abstract::The sensitivity of the dopaminergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after apomorphine (0.5 mg SC), was studied in 11 chronic schizophrenic in-patients under long-term neuroleptic (NL) therapy and after 12 and 30 days' drug withdrawal. GH peak levels after a 12-day drug-free p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00555228
更新日期:1984-01-01 00:00:00
abstract::Active uptake of serotonin by blood platelets of acute schizophrenic patients has been compared to that of a control group. Preliminary results presented in this article indicate that the uptake of the schizophrenic patients was about 40% lower than that of controls. Patients were followed over a period of 5 weeks wit...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00496061
更新日期:1979-08-08 00:00:00
abstract::Different benzodiazepines, when administered to fasting cats, increased both the total amount of food eaten and also the rate at which food was ingested. Moreover, when injected to foodsatiated cats, these compounds made them resume eating voraciously. Pentobarbital also stimulated food intake, but was much less poten...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00428710
更新日期:1976-05-05 00:00:00