Abstract:
RATIONALE:Psychopharmacology needs novel quantitative measures and theoretical approaches based on computational modelling that can be used to help translate behavioural findings from experimental animals to humans, including patients with neuropsychiatric disorders. OBJECTIVES:This brief review exemplifies this approach when applied to recent published studies of the effects of manipulating central dopaminergic and serotoninergic systems in rodents and marmoset monkeys, and possible comparisons with healthy human volunteers receiving systemic agents or patients with depression and schizophrenia. METHODS:Behavioural effects of central depletions of dopamine or serotonin in monkeys in probabilistic learning paradigms are characterised further by computational modelling methods and related to rodent and human data. RESULTS:Several examples are provided of the power of computational modelling to derive new measures and reappraise conventional explanations of regional neurotransmitter depletion and other drug effects, whilst enhancing construct validation in patient groups. Specifically, effects are shown on such parameters as 'stimulus stickiness' and 'side stickiness', which occur over and above effects on standard parameters of reinforcement learning, reminiscent of some early innovations in data analysis in psychopharmacology. CONCLUSIONS:Computational modelling provides a useful methodology for further detailed analysis of behavioural mechanisms that are affected by pharmacological manipulations across species and will aid the translation of experimental findings to understand the therapeutic effects of medications in neuropsychiatric disorders, as well as facilitating future drug discovery.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Robbins TW,Cardinal RNdoi
10.1007/s00213-019-05302-3subject
Has Abstractpub_date
2019-08-01 00:00:00pages
2295-2305issue
8eissn
0033-3158issn
1432-2072pii
10.1007/s00213-019-05302-3journal_volume
236pub_type
杂志文章,评审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:Neurobiological models of addiction suggest that abnormalities of brain reward circuitry distort salience attribution and inhibitory control processes, which in turn contribute to high relapse rates. OBJECTIVES:The aim of this study is to determine whether impairments of salience attribution and inhibitory c...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1975-8
更新日期:2010-12-01 00:00:00
abstract:RATIONALE:Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats. OBJECTIVE:This study examined the effect of cocaine self-administration on behavioral indices of sleep and ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3101-1
更新日期:2013-09-01 00:00:00
abstract:RATIONALE:It has been proposed that brain aldehyde dehydrogenase (ALDH) plays a role in the modulation of some psychopharmacological effects of ethanol. Diethyldithiocarbamate (DDTC), an ALDH inhibitor, elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4-MP)...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-001-0991-0
更新日期:2002-04-01 00:00:00
abstract::Rats injected with doses of d-amphetamine 0--5.0 mg/kg were observed continuously in either an enclosed Y-maze or on an elevated Y-shaped platform. Patterns of increased walking and stereotypy were unaffected by the type of apparatus, but rearing remained totally suppressed at all dose levels on the elevated platform....
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00431954
更新日期:1979-04-25 00:00:00
abstract::In a test of conditioned punishment, saline-treated controls showed a moderate bias in responding away from a lever producing a response-contingent auditory conditioned stimulus (CS) that had been paired with mild footshock during training and towards a lever producing a neutral auditory CS. Systemic treatment with th...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050174
更新日期:1997-01-01 00:00:00
abstract::The present study employed an animal model of drug relapse in which previously extinguished heroin self-administration behavior was reinstated following a single reinforced trial. Male albino rats were trained to traverse a straight-alley for a reinforcer consisting of a single IV injection of 0.06 mg/kg diacetylmorph...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246658
更新日期:1996-04-01 00:00:00
abstract::This study was conducted in order to investigate the level of amitriptyline (AT) and its metabolites. Three separate experiments were carried out. In two of these experiments, rats were treated over 7 days with IP doses of AT (10 mg/kg in experiment A and 2 X 20 mg/kg in experiment C). The rats were sacrificed either ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00431455
更新日期:1984-01-01 00:00:00
abstract::Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in to...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427899
更新日期:1985-01-01 00:00:00
abstract::Cebus apella monkeys were chronically administered the antipsychotic drug fluphenazine decanoate for periods ranging from 3.5 to 5.5 years. In the present study, four of these monkeys and two controls were tested for cognitive abilities on a spatial learning task, which consisted of an original discrimination and four...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00439554
更新日期:1989-01-01 00:00:00
abstract:RATIONALE:Although environmental enrichment renders rats more sensitive to the neurobehavioral effects of acute amphetamine, a previous study found that enriched rats self-administer less amphetamine than isolated rats at a low unit dose (0.03 mg/kg per infusion). In that study, however, acquisition of self-administrat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1134-y
更新日期:2002-08-01 00:00:00
abstract::Recent studies suggest that glucose enhances memory in rodents and humans. The present experiment investigated the effects of glucose on memory performance and blood glucose changes in young adults (19-25 years). Subjects ingested (300 ml beverage) three doses of glucose (0, 30, 100 g) in a random, double-blind, tripl...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02244373
更新日期:1991-01-01 00:00:00
abstract:RATIONALE:Drug development is a high-risk and high failure enterprise, and studies that provide an early read on the pharmacodynamic activity of novel compounds could save time and money, increasing the efficiency of the drug development process. OBJECTIVE:Preclinical and clinical experiments were designed to examine ...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2456-4
更新日期:2012-03-01 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:RATIONALE:Microinjections of ethanol and acetaldehyde into ventral tegmental area (VTA) produce locomotor activation in rats through mechanisms dependent on the mu-opioid receptors. However, it is not clear how these drugs can interact with these receptors. It has been hypothesized that salsolinol could be the responsi...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-009-1751-9
更新日期:2010-03-01 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:Anticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined. OBJECTIVE:The potential of cannabidiol (CBD) and the fatty a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-007-0970-1
更新日期:2008-02-01 00:00:00
abstract:RATIONALE:A deficit in attention and information processing has been considered a central feature in schizophrenia, which might lead to stimulus overload and cognitive fragmentation. It has been shown that patients with schizophrenia display a relative inability to gate incoming stimuli. Thus, patients repeatedly subje...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-004-1901-z
更新日期:2004-11-01 00:00:00
abstract:RATIONALE:The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy ha...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-016-4464-x
更新日期:2017-02-01 00:00:00
abstract:RATIONALE:The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans. OBJECTIVES:To evaluate the effect...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-007-0957-y
更新日期:2008-02-01 00:00:00
abstract:RATIONALE:Previous studies have shown that buspirone, a partial 5-HT(1A) receptor agonist, produces antinociceptive effects in rats and mice; Ca(2+) plays a critical role as a second messenger in mediating nociceptive transmission. 5-HT(1A) receptors have been proven to be coupled functionally with various types of Ca(...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1327-4
更新日期:2003-03-01 00:00:00
abstract:RATIONALE:Inattentional blindness (IB) is the inability to detect a salient yet unexpected task irrelevant stimulus in one's visual field when attention is engaged in an ongoing primary task. The present study is the first to examine the impact of both task difficulty and alcohol consumption on IB and primary task perf...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4772-9
更新日期:2018-01-01 00:00:00
abstract::Dopamine (DA), injected unilaterally into rat forebrain after pretreatment with a monoamine oxidase inhibitor, equipotently induced locomotor arousal when placed in the nucleus accumbens septi (a limbic site) and contralateral deviation of the head when placed in the corpus striatum (an extrapyramidal target); testing...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244285
更新日期:1991-01-01 00:00:00
abstract::The effects of pindolol on the prolactin (PRL) and growth hormone (GH) responses to intravenous tryptophan (LTP) were studied in eight healthy male volunteers. Pindolol pretreatment (40 mg over 48 h) markedly attenuated the GH response to LTP and modestly, but significantly, reduced the LTP-induced increase in plasma ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244090
更新日期:1991-01-01 00:00:00
abstract::Nicotine (6 mg/kg/day) was administered subcutaneously via Alzet osmotic pumps to rats for 28 days. Nociception was measured by the hot-plate and tail-flick methods. A significant antinociceptive effect was demonstrated during the first week of the treatment; after that tolerance developed, lasting for the remaining p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245428
更新日期:1992-01-01 00:00:00
abstract::Two experiments were conducted to test the hypothesis that tolerance to the hypothermic effect of ethanol fails to develop if rats are denied the unconditional stimulus represented by hypothermia. In both experiments, rats were injected with either ethanol (1.9 or 2.5 g/kg) or saline and given microwave hyperthermia (...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00175187
更新日期:1986-01-01 00:00:00
abstract:RATIONALE:Despite the critical role attributed to phosphorylated extracellular signal regulated kinase (pERK1/2) in the nucleus accumbens (Acb) in the actions of addictive drugs, the effects of morphine on ERK1/2 phosphorylation in this area are still controversial. OBJECTIVES:In order to investigate further this issu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-016-4340-8
更新日期:2016-08-01 00:00:00
abstract:RATIONALE:Ketamine, a well-known general dissociative anesthetic agent that is a non-competitive antagonist of the N-methyl-D-aspartate receptor, perturbs the perception of elapsed time and the expectation of upcoming events. OBJECTIVE:The objective of this study was to determine the influence of ketamine on temporal ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05706-6
更新日期:2021-02-01 00:00:00
abstract::Effects of the dopamine D2 receptor antagonist sulpiride and the D1 antagonist SCH-23390 were examined, in rats, in two-bottle preference tests (sucrose versus water) and in single-bottle tests, at different sucrose concentrations. Both drugs decreased sucrose intake in single bottle tests, at low sucrose concentratio...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00634461
更新日期:1989-01-01 00:00:00
abstract:RATIONALE:Available neurochemical probes that lower brain dopamine (DA) levels in man are limited by their tolerability and efficacy. For instance, the acute lowering of brain tyrosine is well tolerated, but only modestly lowers brain DA levels. Modification of tyrosine depletion to robustly lower DA levels would provi...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-2977-0
更新日期:2013-05-01 00:00:00