Further studies of the reinforcing effects of benztropine analogs in rhesus monkeys.


RATIONALE:Several halogenated analogs of benztropine (BZT) have previously been characterized as potent DA uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. In a previous study using a fixed-ratio 10 schedule, two chloro-analogs (3'-Cl-BZT and 4'-Cl-BZT) maintained i.v. self-administration in monkeys but appeared to be weak positive reinforcers. OBJECTIVES:The present experiments were designed to test the hypothesis that 3'-Cl-BZT and 4'-Cl-BZT are relatively weak reinforcers by evaluating reinforcing effects under increased response requirements. To examine further the effect of this halogen substitution on self-administration, 3',4"-diCl-BZT was also evaluated for reinforcing effects. METHODS:Four rhesus monkeys self-administered cocaine (0.03 mg/kg per injection, i.v.) under a fixed-ratio 25 (FR25) schedule until stable responding was established. Saline, various doses of cocaine (0.003-0.2 mg/kg per injection), the BZT analogs (0.012-0.2 mg/kg per injection), GBR 12909 (0.012-0.2 mg/kg per injection), and compounds with known reinforcing effects (d-amphetamine, morphine, pentobarbital, ketamine) were then made available for self-administration. Various doses (0.01-0.3 mg/kg per injection) of the compounds that maintained self-administration under the FR schedule were then substituted for cocaine (0.1 mg/kg per injection) under progressive-ratio (PR) schedules. RESULTS:Reinforcing effects were evident under the FR schedule for 3'-Cl-BZT, 4'-Cl-BZT, GBR 12909, and the control compounds, but not by 3',4"-diCl-BZT. Results with the PR suggested that the rank order of these compounds for their effectiveness as reinforcers was cocaine > GBR 12909 > 3'-Cl-BZT = 4'-Cl-BZT > 3',4"-diCl-BZT. CONCLUSIONS:This study confirms and extends previous results suggesting that compounds with high DAT affinity can have strong, moderate, weak, or no effectiveness as reinforcers. The mechanisms that may underlie this variation in reinforcing effectiveness of these DAT ligands remain to be established.




Woolverton WL,Hecht GS,Agoston GE,Katz JL,Newman AH




Has Abstract


2001-04-01 00:00:00












  • Cognitive performance in depressed patients after chronic use of antidepressants.

    abstract:RATIONALE:Depressive disorders are conditions that often require continuous treatment, and it is therefore important to evaluate the consequences of prolonged administration. There are few studies assessing cognitive functions of depressed patients after long-term use of antidepressants. OBJECTIVES:This study evaluate...


    pub_type: 杂志文章


    authors: Gorenstein C,de Carvalho SC,Artes R,Moreno RA,Marcourakis T

    更新日期:2006-03-01 00:00:00

  • The effects of morphine and scopolamine on auditory discrimination in squirrel monkeys.

    abstract::In squirrel monkeys trained to discriminate between two tones, morphine consistently increased the percent of response failures during tone periods; however, it had no consistent effect on the percent correct responses. In contrast, scopolamine decreased percent correct responses as well as increasing percent response...


    pub_type: 杂志文章


    authors: Milar KS,Dykstra LA

    更新日期:1985-01-01 00:00:00

  • Immobilization stress-induced oral opioid self-administration and withdrawal in rats: role of conditioning factors and the effect of stress on "relapse" to opioid drugs.

    abstract::The effect of 15 min/day of immobilization (IM) stress on oral self-administration (SA) of morphine (0.5 mg/ml) or fentanyl (25 micrograms/ml) and withdrawal was examined in rats. In addition, the role of conditioning factors in these effects was assessed. For each drug, four groups of subjects were exposed for 50 day...


    pub_type: 杂志文章


    authors: Shaham Y

    更新日期:1993-01-01 00:00:00

  • CP-154,526, a CRF type-1 receptor antagonist, attenuates the cue-and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior in rats.

    abstract:RATIONALE:Previous studies from our laboratory and others have indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the extinction/reinstatement animal model of cocaine relapse OBJECTIVE:This present study was designed to investigate the potential role for the HPA axis in the cue- and methamphetamine-i...


    pub_type: 杂志文章


    authors: Moffett MC,Goeders NE

    更新日期:2007-02-01 00:00:00

  • Interaction study between remoxipride and biperiden.

    abstract::Twelve healthy male volunteers took part in a double-blind randomised cross-over study composed of three treatment sessions: remoxipride 100 mg; remoxipride 100 mg plus biperiden 4 mg; and biperiden 4 mg. Plasma and urine concentrations of remoxipride and biperiden, plasma prolactin levels, salivary flow and adverse e...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Yisak W,Farde L,von Bahr C,Nilsson LB,Fredriksson G,Ogenstad S

    更新日期:1993-01-01 00:00:00

  • Translating the smoking cessation properties of the antidepressant nortriptyline using reinforcing, discriminative and aversive stimulus effects of nicotine in rats.

    abstract:RATIONALE:The antidepressant nortriptyline is a second-line pharmacotherapy for smoking cessation. Given that there is limited preclinical data available on the effects of nortriptyline on responses to nicotine, the present study sought to evaluate its effects on the reinforcing, discriminative stimulus (DS) and aversi...


    pub_type: 杂志文章


    authors: Wing VC,Shoaib M

    更新日期:2012-02-01 00:00:00

  • Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine.

    abstract:RATIONALE:Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine...


    pub_type: 杂志文章


    authors: Chen H,Wu J,Zhang J,Fujita Y,Ishima T,Iyo M,Hashimoto K

    更新日期:2012-07-01 00:00:00

  • Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

    abstract:RATIONALE:Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. OBJECTIVE:Employ functional magnetic resonance imaging (f...


    pub_type: 杂志文章,随机对照试验


    authors: Kareken DA,Dzemidzic M,Wetherill L,Eiler W 2nd,Oberlin BG,Harezlak J,Wang Y,O'Connor SJ

    更新日期:2013-07-01 00:00:00

  • Inhibition of brain dopa-decarboxylase by RO 4-4602 infused ICV blocks alcohol drinking induced in rats by cyanamide.

    abstract::Following the stereotaxic implantation of chronic cannulae for intracerebroventricular (ICV) infusion, rats were given an alcohol preference test to establish their preferred concentration in comparison with water. After alcohol was removed, 15 mg/kg cyanamide was then injected subcutaneously for 4 days in order to ma...


    pub_type: 杂志文章


    authors: Miñano FJ,Myers RD

    更新日期:1989-01-01 00:00:00

  • Deep brain stimulation for the treatment of addiction: basic and clinical studies and potential mechanisms of action.

    abstract:RATIONALE:Deep brain stimulation (DBS) has achieved substantial success as a treatment for movement disorders such as Parkinson's disease. The therapeutic efficacy and relative lack of serious side effects resulted in the expansion of DBS into the treatment of many other diseases, including obsessive-compulsive disorde...


    pub_type: 杂志文章,评审


    authors: Pierce RC,Vassoler FM

    更新日期:2013-10-01 00:00:00

  • Savoxepine fails to selectively influence glucose metabolism in the rat limbic system.

    abstract::The [14C]-2-deoxyglucose method was used to map the in vivo metabolic response of glucose to savoxepine, a novel tetracyclic cyano-dibenzoxepino-azepine. Savoxepine is reported to have higher affinity for dopamine (DA) receptors in the hippocampus than in the striatum and hence should have dose-dependent, anatomically...


    pub_type: 杂志文章


    authors: Cascella NG,Tarazi FI,Shirakawa O,Tamminga CA

    更新日期:1994-03-01 00:00:00

  • Facilitation by dexamethasone of tolerance to ethanol in the rat.

    abstract::The purpose of this study was to examine the relationship between the development of tolerance to ethanol and the hypothalamic-pituitary-adrenal cortex (H-P-AC) system by modifying the H-P-AC system through the use of a synthetic glucocorticoid, dexamethasone. Also this study determined whether repeated drug administr...


    pub_type: 杂志文章


    authors: Wood WG

    更新日期:1977-03-23 00:00:00

  • Limited stimulus generalization between delta 9-THC and diazepam in pigeons and gerbils.

    abstract::Pigeons trained to discriminate between the presence and absence of delta 9-THC (0.56 mg/kg, IM, intramuscularly) were tested with diazepam (5.6-30 mg/kg), administered IG (intragastrically), and were found to generalize the response associated with the THC training to the diazepam treatment only to a limited extent. ...


    pub_type: 杂志文章


    authors: Järbe TU,Hiltunen AJ

    更新日期:1988-01-01 00:00:00

  • Potentiation of ethanol withdrawal by prior dependence.

    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...


    pub_type: 杂志文章


    authors: Baker TB,Cannon DS

    更新日期:1979-01-31 00:00:00

  • Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress.

    abstract:RATIONALE:Severe, traumatic stress or repeated exposure to stress can result in long-term deleterious effects, including hippocampal cell atrophy and death, which, in turn, result in memory impairments and behavioural abnormalities. The dopaminergic D(2) receptor agonist, bromocriptine, has been shown to modulate learn...


    pub_type: 杂志文章


    authors: Srikumar BN,Raju TR,Shankaranarayana Rao BS

    更新日期:2007-08-01 00:00:00

  • Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels.

    abstract::Antipsychotic drugs, such as haloperidol and risperidone, are used in long-term treatment of psychiatric patients and thus increase the risk of obesity and other metabolic dysfunctions. Available evidence suggests that these drugs have pro-inflammatory effect, which contributes to the establishment of endocrine distur...


    pub_type: 杂志文章


    authors: da Cruz Jung IE,Machado AK,da Cruz IB,Barbisan F,Azzolin VF,Duarte T,Duarte MM,do Prado-Lima PA,Bochi GV,Scola G,Moresco RN

    更新日期:2016-05-01 00:00:00

  • A randomized, 12-week study of the effects of extended-release paliperidone (paliperidone ER) and olanzapine on metabolic profile, weight, insulin resistance, and β-cell function in schizophrenic patients.

    abstract:OBJECTIVE:To compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. METHODS:Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At baseline and ever...


    pub_type: 杂志文章,随机对照试验


    authors: Hu S,Yao M,Peterson BS,Xu D,Hu J,Tang J,Fan B,Liao Z,Yuan T,Li Y,Yue W,Wei N,Zhou W,Huang M,Xu Y

    更新日期:2013-11-01 00:00:00

  • Acute effects of methadone on EEG power spectrum and event-related potentials among heroin dependents.

    abstract::Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain...


    pub_type: 杂志文章


    authors: Motlagh F,Ibrahim F,Rashid R,Shafiabady N,Seghatoleslam T,Habil H

    更新日期:2018-11-01 00:00:00

  • Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.

    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...


    pub_type: 杂志文章


    authors: Xu H,Das S,Sturgill M,Hodgkinson C,Yuan Q,Goldman D,Grasing K

    更新日期:2017-08-01 00:00:00

  • Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using a rodent five-choice reaction time task.

    abstract:RATIONALE:Converging evidence suggests that dopaminergic and serotonergic mechanisms affect distinct aspects of cognitive performance. Experiments using the rodent five-choice reaction time task have established a critical role for dopaminergic mechanisms in the rat medial prefrontal cortex (mPFC), but have yielded onl...


    pub_type: 杂志文章


    authors: Passetti F,Dalley JW,Robbins TW

    更新日期:2003-01-01 00:00:00

  • Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus).

    abstract:RATIONALE:There is a requirement to ensure that UK armed forces are provided with the best possible medical countermeasures to prevent or mitigate the effects of exposure to nerve agents. When pretreatments are under consideration, it is of particular importance to ensure that they do not in themselves give rise to adv...


    pub_type: 杂志文章


    authors: Muggleton NG,Bowditch AP,Crofts HS,Scott EA,Pearce PC

    更新日期:2003-03-01 00:00:00

  • CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.

    abstract:RATIONALE:The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might ...


    pub_type: 杂志文章


    authors: Morisot N,Millan MJ,Contarino A

    更新日期:2014-10-01 00:00:00

  • Serotonin-induced platelet intracellular calcium mobilization in depressed patients.

    abstract::Serotonin(5-HT)-stimulated intracellular calcium(Ca) mobilization was measured in the platelets of depressed patients to assess 5-HT2 receptor function. The 5-HT-induced Ca response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancho...


    pub_type: 临床试验,杂志文章


    authors: Kusumi I,Koyama T,Yamashita I

    更新日期:1994-01-01 00:00:00

  • Reversal of ethanol intoxication in humans: an assessment of the efficacy of L-dopa, aminophylline, and ephedrine.

    abstract::The effect of postethanol treatment with L-Dopa, aminophylline and/or ephedrine was investigated. In one experiment, healthy, male, moderate drinkers ingested ethanol (0.8 g/kg) and then either L-Dopa (1.5 g), or placebo. In a second experiment, subjects ingested ethanol followed by aminophylline (200 mg), ephedrine (...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Alkana RL,Parker ES,Cohen HB,Birch H,Noble EP

    更新日期:1977-12-28 00:00:00

  • Discriminative stimulus properties of phenytoin in the pigeon.

    abstract::Pigeons trained under a two-key drug discrimination procedure eventually learned to discriminate 5 mg/kg phenytoin from saline injections. When 1.25-20 mg/kg doses of phenytoin were substituted for the training dose, the percentage of responses directed to the phenytoin-appropriate key varied directly with dose. Chlor...


    pub_type: 杂志文章


    authors: Krafft K,Cleary J,Poling A

    更新日期:1983-01-01 00:00:00

  • Sedative and electroencephalographic actions of erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA): relationship to inhibition of brain adenosine deaminase.

    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...


    pub_type: 杂志文章


    authors: Mendelson WB,Kuruvilla A,Watlington T,Goehl K,Paul SM,Skolnick P

    更新日期:1983-01-01 00:00:00

  • Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme.

    abstract:RATIONALE:Alzheimer disease (AD), a progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of AD, and thus, treatment strategies should address impairments in both systems. Evidence sugges...


    pub_type: 杂志文章,评审


    authors: Schaeffer EL,Gattaz WF

    更新日期:2008-05-01 00:00:00

  • Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers.

    abstract:RATIONALE:It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. OBJECTIVES:Using a high-dose carbon dioxide (CO(2)) challenge, we aimed to investigate the eff...


    pub_type: 杂志文章,随机对照试验


    authors: Colasanti A,Esquivel G,den Boer E,Horlings A,Dandachi A,Oostwegel JL,van Donkelaar EL,Griez EJ,Schruers K

    更新日期:2011-06-01 00:00:00

  • Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone.

    abstract::The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective...


    pub_type: 杂志文章


    authors: Naik SR,Naid PR,Sheth UK

    更新日期:1978-04-14 00:00:00

  • Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways.

    abstract:RATIONALE AND OBJECTIVES:Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models ...


    pub_type: 杂志文章,评审


    authors: Krasnova IN,Justinova Z,Cadet JL

    更新日期:2016-05-01 00:00:00