Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats.

Abstract:

RATIONALE:3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT). OBJECTIVES:We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV. METHODS:To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats. RESULTS:MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT. CONCLUSIONS:Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.

journal_title

Psychopharmacology

authors

Schindler CW,Thorndike EB,Goldberg SR,Lehner KR,Cozzi NV,Brandt SD,Baumann MH

doi

10.1007/s00213-015-4057-0

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

1981-90

issue

10

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-015-4057-0

journal_volume

233

pub_type

杂志文章
  • Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study.

    abstract:RATIONALE:Heavy ecstasy use in humans has been associated with cognitive impairments and changes in cognitive brain function supposedly due to damage to the serotonin system. There is concern that even a single dose of 3,4-methylenedioxymethamphetamine may be neurotoxic, but very little is known about the consequences ...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00213-007-0792-1

    authors: Jager G,de Win MM,Vervaeke HK,Schilt T,Kahn RS,van den Brink W,van Ree JM,Ramsey NF

    更新日期:2007-08-01 00:00:00

  • Assessing physiological dependence and withdrawal potential of mitragynine using schedule-controlled behaviour in rats.

    abstract:RATIONALE:Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG). OBJECTIVES:This study examined the dependence-producing effects of MG using operant-scheduled behaviour in ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-019-05418-6

    authors: Harun N,Johari IS,Mansor SM,Shoaib M

    更新日期:2020-03-01 00:00:00

  • Urinary 4-hydroxy-3-methoxyphenylglycol is not a predictor for clinical response to amitriptyline in depressive illness.

    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

    authors: Coppen A,Rama Rao VA,Ruthven CR,Goodwin BL,Sandler M

    更新日期:1979-06-28 00:00:00

  • Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake suppressant effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI).

    abstract::Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) to rats produced dose-related decreases in 1-h food intake in the food-deprived paradigm. Pretreatment with spiperone (5-HT1A/5-HT2/D2 antagonist), propranolol or CGP361A (beta-adrenoceptor antagonists that also have binding affinit...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02247721

    authors: Aulakh CS,Hill JL,Yoney HT,Murphy DL

    更新日期:1992-01-01 00:00:00

  • Predictive validity of the extinction/reinstatement model of drug craving.

    abstract::The effects of chronic desmethylimipramine (DMI) treatment on measures of incentive motivation for cocaine were assessed in order to investigate the predictive validity of the extinction/reinstatement model of drug craving. Rats were trained to respond for cocaine infusions (0.75 mg/kg per 0.1 ml i.v.) or received yok...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s002130050496

    authors: Fuchs RA,Tran-Nguyen LT,Specio SE,Groff RS,Neisewander JL

    更新日期:1998-01-01 00:00:00

  • Influence of nicotine on simulator flight performance in non-smokers.

    abstract::In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s002130050736

    authors: Mumenthaler MS,Taylor JL,O'Hara R,Yesavage JA

    更新日期:1998-11-01 00:00:00

  • Activation of forebrain dopamine systems by phencyclidine and footshock stress: evidence for distinct mechanisms.

    abstract::Phencyclidine combined with footshock stress produced a greater increase in the homovanillic acid content of prefrontal cortex than either phencyclidine or footshock alone. Phencyclidine decreased both substance P and substance K in the ventral tegmental area. The results suggest that phencyclidine and footshock activ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02439600

    authors: Bowers MB Jr,Bannon MJ,Hoffman FJ Jr

    更新日期:1987-01-01 00:00:00

  • Effects of three therapeutic doses of codeine/paracetamol on driving performance, a psychomotor vigilance test, and subjective feelings.

    abstract:RATIONALE:Some recent pharmacoepidemiological studies revealed an elevated risk of driving accidents after opioid analgesics uses. Among analgesics, codeine is often associated with paracetamol in numerous pharmaceutical specialties. OBJECTIVES:The objective of this study was to evaluate the dose-effect relationship o...

    journal_title:Psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00213-013-3035-7

    authors: Amato JN,Marie S,Lelong-Boulouard V,Paillet-Loilier M,Berthelon C,Coquerel A,Denise P,Bocca ML

    更新日期:2013-07-01 00:00:00

  • Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine.

    abstract::Cortical and hippocampal EEGs in animal models of schizophrenia were compared to those obtained with psychotomimetics or antipsychotic agents by utilizing power spectral analysis. Models of positive schizophrenic symptoms were created with methamphetamine (MAP) and cocaine, and a model of both negative and positive sy...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s002130050306

    authors: Yamamoto J

    更新日期:1997-06-01 00:00:00

  • Human tolerance to alcohol: the role of Pavlovian conditioning processes.

    abstract::To test the Pavlovian conditioning model of alcohol tolerance, two groups of eight male social drinkers each received five administrations of alcohol and five administrations of an equal volume of tonic each, on an alternating basis, during the initial 10-session tolerance development phase of the study. Group 1 recei...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00310519

    authors: Shapiro AP,Nathan PE

    更新日期:1986-01-01 00:00:00

  • Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers.

    abstract::The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12 healthy volunteers. Subjects ingested placebo, morphine 20 or 40 mg, or codeine 60 or 120 mg in a randomized, double-blind, crossover design. The smaller and larger doses of each drug were putativ...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s002130050757

    authors: Walker DJ,Zacny JP

    更新日期:1998-11-01 00:00:00

  • Single dose of a dopamine agonist impairs reinforcement learning in humans: behavioral evidence from a laboratory-based measure of reward responsiveness.

    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

    authors: Pizzagalli DA,Evins AE,Schetter EC,Frank MJ,Pajtas PE,Santesso DL,Culhane M

    更新日期:2008-02-01 00:00:00

  • Pharmacological and behavioral characterization of cocaine-kindled seizures in mice.

    abstract:RATIONALE:Convulsions associated with cocaine toxicity are a serious aspect of cocaine-related emergency room incidents. Seizures can result from a single high dose of cocaine, and evidence is accumulating that correlates repetitive administration of sub-convulsive doses of cocaine with a decreased seizure threshold, a...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s002130050027

    authors: Miller KA,Witkin JM,Ungard JT,Gasior M

    更新日期:2000-01-01 00:00:00

  • Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects.

    abstract:RATIONALE:The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with citicoline decreased self-reported desire to use cocaine in crack cocaine users. OBJECTIVE:The present study w...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s002130100824

    authors: Lukas SE,Kouri EM,Rhee C,Madrid A,Renshaw PF

    更新日期:2001-09-01 00:00:00

  • The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys.

    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

    authors: Brutcher RE,Nader MA

    更新日期:2013-09-01 00:00:00

  • Influence of morphine sensitization on the responsiveness of mesolimbic and mesocortical dopamine transmission to appetitive and aversive gustatory stimuli.

    abstract:RATIONALE:Repeated treatment with morphine has been shown to sensitize rats to its stimulant effects on motor activity and mesolimbic dopamine (DA) transmission. OBJECTIVES:The aim of this study is to investigate if morphine sensitization is associated to changes in the behavioral reactions to appetitive and aversive ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-011-2220-9

    authors: De Luca MA,Bimpisidis Z,Bassareo V,Di Chiara G

    更新日期:2011-08-01 00:00:00

  • Behavioural effects of selective mu-, kappa-, and delta-opioid agonists in neonatal rats.

    abstract::The behavioural effects of selective mu-, kappa- and delta-opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to mu-agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (D-Ala2, NMe-Phe4, Glyol5-enkephalin) produced overt s...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00439459

    authors: Jackson HC,Kitchen I

    更新日期:1989-01-01 00:00:00

  • Non-competitive inhibition of clomipramine N-demethylation by fluvoxamine.

    abstract::The selective serotonin reuptake inhibitor fluvoxamine interferes with the metabolism of tricyclic antidepressants. The present investigation was set out to characterize these interactions in vitro using rat liver microsomes and in vivo by analysing levels of clomipramine and metabolites in sera of depressed patients ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02245180

    authors: Härtter S,Arand M,Oesch F,Hiemke C

    更新日期:1995-01-01 00:00:00

  • Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABAA receptor subtypes.

    abstract:RATIONALE:Benzodiazepine agonists characteristically increase food intake in humans and non-human subjects, and the underlying mechanisms of this effect are not understood completely. OBJECTIVE:Compounds with selectivity for GABAA receptor subtypes were used to evaluate the role of GABAA receptors containing alpha1 an...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-006-0431-2

    authors: Duke AN,Platt DM,Cook JM,Huang S,Yin W,Mattingly BA,Rowlett JK

    更新日期:2006-08-01 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...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-018-5035-0

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

    更新日期:2018-11-01 00:00:00

  • Cognitive-impairing effects of medroxyprogesterone acetate in the rat: independent and interactive effects across time.

    abstract:RATIONALE:The synthetic progestin medroxyprogesterone acetate (MPA), widely used in hormone therapy (HT) and as the contraceptive Depo Provera, is implicated in detrimental cognitive effects in women. Recent evidence in aged ovariectomized (Ovx) rodents shows that short-term MPA treatment impairs cognition and alters t...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-011-2322-4

    authors: Braden BB,Garcia AN,Mennenga SE,Prokai L,Villa SR,Acosta JI,Lefort N,Simard AR,Bimonte-Nelson HA

    更新日期:2011-11-01 00:00:00

  • Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.

    abstract:RATIONALE:Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. OBJECTIVES:To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00213-006-0622-x

    authors: Gunes A,Scordo MG,Jaanson P,Dahl ML

    更新日期:2007-03-01 00:00:00

  • Role of nicotinic receptors in the lateral habenula in the attenuation of amphetamine-induced prepulse inhibition deficits of the acoustic startle response in rats.

    abstract:RATIONALE:Prepulse inhibition (PPI) refers to the reduction of the startle response magnitude when a startling stimulus is closely preceded by a weak stimulus. PPI is commonly used to measure sensorimotor gating. In rats, the PPI reduction induced by the dopamine agonist apomorphine can be reversed by systemic administ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-015-3940-z

    authors: Larrauri JA,Burke DA,Hall BJ,Levin ED

    更新日期:2015-08-01 00:00:00

  • In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro.

    abstract::Lu 25-109 [5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1-methylpyridine] , has M agonistic and M2/M3 antagonistic effects at muscarinic receptors in vitro; a pharmacological profile that may be beneficial in treatment of Alzheimer's disease. In the present study, we compare functional in vivo effects of Lu 25-109 ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s002130050615

    authors: Sánchez C,Arnt J,Didriksen M,Dragsted N,Moltzen Lenz S,Matz J

    更新日期:1998-06-01 00:00:00

  • MK-801 can facilitate passive avoidance memory when retention is not present in control animals, and can fail to facilitate when it is present.

    abstract::The results confirm that NMDA receptor blockade can result in improved retention performance of mice in step-down passive avoidance. A series of behavioural variations and analyses revealed that memory in the task depended mainly on the appearance of the grid that had been associated with shock, rather than on the exe...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02244300

    authors: Weiskrantz L,Mondadori C

    更新日期:1991-01-01 00:00:00

  • Learning impairment in the radial-arm maze following prolonged cannabis treatment in rats.

    abstract::Chronic oral administration of cannabis extract to rats (daily delta 9-tetrahydrocannabinol dose 20 mg/kg) was examined in three experiments for its residual effect on radial-arm maze learning following a 1-month drug-free period. Learning a simple eight-arm maze was significantly impaired in rats treated for either 6...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00431932

    authors: Stiglick A,Kalant H

    更新日期:1982-01-01 00:00:00

  • The relationship between level of cigarette consumption and latency to the onset of retrospectively reported withdrawal symptoms.

    abstract:RATIONALE:Subthreshold smokers (who smoke < or =5 cigarettes/day) experience withdrawal symptoms, yet they smoke less than is required to maintain serum nicotine levels. OBJECTIVES:For study 1, our aim was to determine (1) if adult subthreshold smokers report withdrawal symptoms; (2) how they rate symptom severity; (3...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-006-0497-x

    authors: Fernando WW,Wellman RJ,Difranza JR

    更新日期:2006-10-01 00:00:00

  • Active vaccination reduces reinforcing effects of MDPV in male Sprague-Dawley rats trained to self-administer cocaine.

    abstract:RATIONALE:3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone abused for its cocaine-like psychostimulant effects in "bath salts" products. While there are currently no pharmacotherapies for MDPV abuse, rodent studies suggest immunotherapy may offer a feasible treatment option. OBJECTIVES:These studies test...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-020-05558-0

    authors: McClenahan SJ,Gunnell MG,Owens SM,Fantegrossi WE

    更新日期:2020-09-01 00:00:00

  • Lithium ions inhibit function of low- but not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115).

    abstract::Murine neuroblastoma cells (clone N1E-115) possess both high- and low-affinity muscarinic receptors. The low-affinity muscarinic receptor, when stimulated, initiates the formation of cyclic GMP by activating the enzyme guanylate cyclase; whereas stimulation of the high-affinity receptor inhibits prostaglanding E1-medi...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00427901

    authors: Kanba S,Pfenning M,Richelson E

    更新日期:1985-01-01 00:00:00

  • The effect of reboxetine co-administration with olanzapine on metabolic and endocrine profile in schizophrenia patients.

    abstract:RATIONALE:We previously demonstrated that the addition of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. Using the same study sample, we also sought to determine whether reboxetine's weight-attenuating effect was accompanied by a beneficial effect on metabolic and ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00213-013-3199-1

    authors: Amrami-Weizman A,Maayan R,Gil-Ad I,Pashinian A,Fuchs C,Kotler M,Poyurovsky M

    更新日期:2013-11-01 00:00:00