Abstract:
RATIONALE:Cocaine dependence is a major health concern and there are no effective pharmacotherapies currently available. Although cocaine is an indirect DA agonist that binds to all three monoamine transporters, there is much evidence implicating a greater role for the dopamine (DAT) than norepinephrine (NET) and serotonin (SERT) transporters in the behavioral effects of cocaine. As such, several groups have developed compounds that exhibit high affinity and selectivity for the DAT. OBJECTIVE:The present investigation examined the cocaine-like discriminative stimulus effects in rats of novel cocaine analogs (RTI 12, 13, 15) and 3-phenyltropane analogs (RTI 111, 112, 113, 114, 117 120, 121, 123, 134 and 152) of which several exhibit high affinity (e.g., <7 nM) and selectivity for the DAT. RESULTS:During dose-effect testing all drugs produced 75-100% cocaine-lever responding. Analyses indicated that the potency of the compounds to produce cocaine-like discriminative stimulus effects was correlated with their affinity for the DAT and the NET but not SERT. Due to the extremely large concentrations (e.g., 10,000-31,024 nM) needed to occupy the NET in vitro, it is doubtful if the doses administered had meaningful NET activity. The selectivity at the DAT, relative to the other transporters, was not indicative of the potency with which these drugs substituted for cocaine. CONCLUSIONS:The cocaine-like discriminative stimulus of the RTI compounds tested appear to be mediated by the DAT, however the extent to which the NET is involved remains unclear. Additionally, several of the RTI compounds had properties consistent with those thought desirable in a pharmacotherapeutic for cocaine dependence.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Cook CD,Carroll IF,Beardsley PMdoi
10.1007/s002130100891subject
Has Abstractpub_date
2001-12-01 00:00:00pages
58-63issue
1eissn
0033-3158issn
1432-2072journal_volume
159pub_type
杂志文章abstract:RATIONALE:Investigations of the neural consequences of the effects of cocaine on cognition have centered on specific brain circuits including prefrontal cortex, medial temporal lobe and striatum and their roles in controlling drug dependent behavior and addiction. These regions are critical to many aspects of drug abus...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-2017-2
更新日期:2011-01-01 00:00:00
abstract::Because of the increasing demand for refined techniques to record drug-induced motoric changes, we designed and evaluated a computer monitoring system with continuous measurement of different parameters of rat motor activity. This system is particularly useful for chronic drug studies because it can characterize patte...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432113
更新日期:1983-01-01 00:00:00
abstract::The effects of various psychomotor stimulant drugs and drugs outside this class were examined on the efficacy of stimuli previously paired with reinforcement or reward (conditioned reinforcers, CR) in controlling responding. Pipradrol (5-45 mumol/kg), d-amphetamine (1.25-15.0 mumol/kg), and the cocaine analogues WIN 3...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427952
更新日期:1983-01-01 00:00:00
abstract:INTRODUCTION:Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-008-1122-y
更新日期:2008-09-01 00:00:00
abstract:RATIONALE:The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. OBJECTIVES:We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predic...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-016-4307-9
更新日期:2016-07-01 00:00:00
abstract:RATIONALE:Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of ...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-017-4793-4
更新日期:2018-02-01 00:00:00
abstract:RATIONALE:Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse. Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues, but the mechanism by which these effects occur remains un...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2610-z
更新日期:2012-06-01 00:00:00
abstract:RATIONALE:Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about t...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2426-x
更新日期:2012-02-01 00:00:00
abstract::Chronic treatment of rats with choline caused a decrease in the hypothermic response to pilocarpine. The action of choline on the muscarinic receptors is consistent with electrophysiological and binding studies, supporting a direct muscarinic action for choline. Administration of direct muscarinic agonists has been sh...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427955
更新日期:1983-01-01 00:00:00
abstract:RATIONALE:One third of US smokers are intermittent smokers (ITS) who do not smoke daily. Unlike daily smokers (DS), whose smoking is negatively reinforced by withdrawal relief, ITS may be motivated by immediate positive reinforcement. In contrast, incentive salience theory posits hypothesis that "liking" of drug effect...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4682-x
更新日期:2017-10-01 00:00:00
abstract::An operant task for the measurement of sustained attention or vigilance in rats was characterized. The task requires the animals to respond to the presentation of visual signals (presented for 25, 50, or 500 ms) by operating one lever ("hits") and to the absence of a signal by operating the opposite lever ("correct re...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246109
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:Preclinical studies suggest that medications enhancing the brain gamma amino butyric acid (GABA) system attenuate the rewarding effects of stimulants including nicotine. These preclinical studies have not been followed up in systematic human studies. OBJECTIVES:This study was conducted to examine the effects...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-005-0010-y
更新日期:2005-09-01 00:00:00
abstract::The low rate of success for identifying effective treatments for cognitive dysfunction has prompted recent efforts to improve pharmaceutical discovery and development. In particular, investigators have emphasized improving translation from pre-clinical to clinical research. A specific area of focus has been touchscree...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-015-4012-0
更新日期:2015-11-01 00:00:00
abstract::To assess the effects of chlordiazepoxide (CDP) on a stable discrimination performance, eight rats were trained on a simple brightness discrimination and injected with three dosages (0, 5, and 10 mg/kg) once performance was stable. Signal detection analysis of the results was used to differentiate sensory from motor/r...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433568
更新日期:1979-06-21 00:00:00
abstract::Chronic exposure to very mild unpredictable stress has previously been found to depress the consumption of, and preference for, highly palatable sweet solutions. The present study used the place conditioning procedure to investigate whether these effects result from a decreased sensitivity to reward. Rats were subject...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244188
更新日期:1991-01-01 00:00:00
abstract::Parenteral administration of the adenosine deaminase (ADA) inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) results in a profound decrease in spontaneous motor activity in mice and rats. The inhibition of cortical ADA activity measured ex vivo parallels the decrease in spontaneous motor activity in a time-depend...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427798
更新日期:1983-01-01 00:00:00
abstract::The effects of serotonergic manipulations on the escape interference engendered by exposure to inescapable shock were assessed. Consistent with the view that the behavioral interference was related to reductions of serotonin (5-HT), treatment with the 5-HT receptor blocker methysergide mimicked the effects of inescapa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00181242
更新日期:1986-01-01 00:00:00
abstract:RATIONALE:Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder. Little is known about fluoxetine's influence on mood changes after quitting smoking, which often resemble sub-clinical depression. OBJECTIVES:The present study, a re-analysis of previously published data ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s00213-003-1711-8
更新日期:2004-04-01 00:00:00
abstract::The concurrent influence of dopaminergic, sigma and muscarinic neurotransmitter systems in mediating cocaine-induced lethality is predicted by previous receptor binding results from our laboratories. The present results demonstrate that pharmacological manipulations of these predicted neurotransmitter systems alter th...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050198
更新日期:1997-02-01 00:00:00
abstract::The influence of mepiprazole (EMD 16,923), a new pyrazol-ylalkyl-piperazine derivative, on the uptake of 3H-norepinephrine (NE), 3H-dopamine (DA), and 3H-serotonin (5-HT) into rat brain synaptosomes from cerebral cortex, corpus striatum, and hypothalamus was investigated in comparison with several psychotropic drugs, ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00496865
更新日期:1976-08-17 00:00:00
abstract::Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneou...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050509
更新日期:1998-02-01 00:00:00
abstract::Ten rats were trained to lever press for food reward on a schedule of differential reinforcement of low rates of response with a 20-s criterion (DRL 20). Ten more were trained on a new schedule of punishment, designed to be comparable to DRL 20 - differential punishment of high rates of response (DPH 20). Under this s...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00431812
更新日期:1985-01-01 00:00:00
abstract::Two experiments were carried out on pigeons to assess the effects of acute ethanol (ETOH) administration on a delayed pair comparison procedure. ETOH disrupted performance at the two higher doses (1.0 and 2.0 g/kg, given orally). When the initial (zero delay) performance levels of treated and untreated birds were equa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00434411
更新日期:1980-01-01 00:00:00
abstract::The effects of meperidine on operant behavioral thermoregulation were investigated using a convective thermal controller and mice trained to alternate at will the thermal-drive condition, changing it from an air flow of 15 degrees C to one of 45 degrees C, and vice versa. Administration of 15 mg/kg meperidine resulted...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00491979
更新日期:1979-09-01 00:00:00
abstract:RATIONALE:Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear. OBJECTIVES:To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gen...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-005-0104-6
更新日期:2005-11-01 00:00:00
abstract::Thirty rats were randomly assigned to three groups. Group 1 was given a 21-day exposure to an ethanol (EtOH) liquid diet, while Groups 2 and 3 were given equivalent amounts of an isocaloric non-EtOH liquid diet. Group 1 rats had withdrawal syndromes following EtOH removal. After a two-week recovery period, Groups 1 an...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432279
更新日期:1979-01-31 00:00:00
abstract:BACKGROUND AND RATIONALE:Pain is a complex sensory experience, involving cognitive factors, environment (setting, society, and culture), experience, and gender and is modulated significantly by the central nervous system (CNS). The mechanisms by which opioid analgesics work are understood, but this class of drugs is no...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-010-1819-6
更新日期:2010-06-01 00:00:00
abstract::Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with nifedipine. Performances during a five-color simultaneous match-to-sample task were measured during three dosing schedules (0.20, 0.68, and 1.14 mg/kg/day) and vehicle. Each do...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245802
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:The serotonin (5-HT) system is involved in pain modulation, and 5-HT receptor agonists can enhance antinociceptive effects of mu opioid receptor agonists. Less is known about the actions of 5-HT receptor agonists on other effects of opioids. OBJECTIVE:This study examined the effects of non-contingent and con...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2803-0
更新日期:2013-01-01 00:00:00
abstract:RATIONALE:Studies have shown that social drinkers are poor estimators of alcohol-induced impairment. Underestimates of blood alcohol concentration and other indices of intoxication are associated with decisions to perform risky behaviors, such as operating a motor vehicle. It is possible that self-evaluations of impair...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00213-004-1964-x
更新日期:2005-02-01 00:00:00