The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of m-chlorophenylpiperazine.


:m-Chlorophenylpiperazine (mCPP), a major metabolite of the atypical antidepressant trazadone, has been observed to produce marked physiological and behavioral effects in both humans and animals. These effects have been attributed to the interaction of mCPP with serotonergic receptors. The present study was designed to characterize those interactions of mCPP with central serotonergic receptors which mediate mCPP-induced stimulus control. A series of serotonergic antagonists (mesulergine, pizotyline, ketanserin, spiperone, risperidone, ritanserin, metergoline, pirenpirone, and LY53857) was tested for the ability to block the mCPP stimulus. The affinity of these antagonists for 5-HT2A and 5-HT2C receptors was then correlated with maximal percent inhibition of the mCPP stimulus. Kd at the 5-HT2C receptor was inversely proportional (r = -0.75, P < 0.05), and Kd at the 5-HT2A receptor directly proportional (r = +0.67, P < 0.05) to the maximal percent inhibition of the mCPP stimulus. The 5-HT2C selectivity ratio [Kd(5-HT2A)/Kd(5-HT2C)] of the antagonists was directly proportional (r = +0.86, P < 0.01) to maximal percent inhibition of the mCPP stimulus. A multiple regressions analysis indicated that 81% of the variance in the ability of a given antagonist to block the mCPP stimulus could be predicted on the basis of its affinity for 5-HT2A and 5-HT2C receptors. It is concluded that the stimulus effects of mCPP are mediated predominantly by a combination of agonist activity at 5-HT2C receptors and antagonist activity at 5-HT2A receptors.




Fiorella D,Rabin RA,Winter JC




Has Abstract


1995-05-01 00:00:00












  • Nicotine delivery to users from cigarettes and from different types of e-cigarettes.

    abstract:BACKGROUND:Delivering nicotine in the way smokers seek is likely to be the key factor in e-cigarette (EC) success in replacing cigarettes. We examined to what degree different types of EC mimic nicotine intake from cigarettes. METHODS:Twelve participants ('dual users' of EC and cigarettes) used their own brand cigaret...


    pub_type: 杂志文章


    authors: Hajek P,Przulj D,Phillips A,Anderson R,McRobbie H

    更新日期:2017-03-01 00:00:00

  • Characterization of the discriminative stimulus effects of buprenorphine in pigeons.

    abstract:RATIONALE:Buprenorphine is a low-efficacy mu opioid agonist that can reduce drug taking in opioid abusers; however, the mechanism by which buprenorphine modifies the actions of other drug taking and the consequences of repeated treatment with buprenorphine are not fully understood. OBJECTIVE:The purposes of this study...


    pub_type: 杂志文章


    authors: Galici R,Brandt MR,France CP

    更新日期:2002-03-01 00:00:00

  • Effect of selective 5-HT1A agonists and 5-HT2 antagonists on inherited catalepsy in rats.

    abstract::The effects of the selective 5-HT1A agonists 8-OH-DPAT and flesinoxan and the selective 5-HT2 antagonists ritanserin and ketanserin on immobility time in rats bred for predisposition to catalepsy have been studied. Treatment with 8-OH-DPAT as well as flesinoxan caused a marked dose-dependent decrease in immobility tim...


    pub_type: 杂志文章


    authors: Kulikov AV,Kolpakov VG,Maslova GB,Kozintsev I,Popova NK

    更新日期:1994-02-01 00:00:00

  • Blockade of NMDA receptors in the prefrontal cortex increases dopamine and acetylcholine release in the nucleus accumbens and motor activity.

    abstract:OBJECTIVES:The present study investigates the effects of injections of a specific N-methyl-D-aspartic acid (NMDA) antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) into the prefrontal cortex (PFC) on the extracellular concentrations of dopamine and acetylcholine in the nucleus accumbens (NAc) and...


    pub_type: 杂志文章


    authors: Del Arco A,Segovia G,Mora F

    更新日期:2008-12-01 00:00:00

  • Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.

    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...


    pub_type: 杂志文章


    authors: Hymowitz N,Brezenoff HE,McGee J,Campbell K,Knight V

    更新日期:1985-01-01 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

  • The effect of varenicline and nicotine patch on smoking rate and satisfaction with smoking: an examination of the mechanism of action of two pre-quit pharmacotherapies.

    abstract:OBJECTIVES:In recent years, there has been growing research interest in using nicotine replacement medications to aid smoking reduction prior to a quit attempt. Gaining a better understanding of how treatments influence smoking reduction may allow for better tailoring of treatments and, ultimately, better cessation out...


    pub_type: 杂志文章


    authors: Lu W,Chappell K,Walters JAE,Jacobson GA,Patel R,Schüz N,Ferguson SG

    更新日期:2017-07-01 00:00:00

  • Inhibitory effect of ritanserin on the 5-hydroxytryptophan-mediated cortisol, ACTH and prolactin secretion in humans.

    abstract::Oral administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan (5-HTP), 200 mg, significantly increased plasma cortisol levels in man. L-5-HTP had no significant effect on the plasma prolactin levels. A borderline effect of 5-HTP on plasma ACTH levels was found. Pretreatment with the 5-HT2/5-HT1c antagoni...


    pub_type: 杂志文章


    authors: Lee MA,Nash JF,Barnes M,Meltzer HY

    更新日期:1991-01-01 00:00:00

  • A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the treatment of schizophrenia.

    abstract::Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dop...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: King DJ,Link CG,Kowalcyk B

    更新日期:1998-05-01 00:00:00

  • Attenuation of delta 9-tetrahydrocannabinol-induced withdrawal-like behaviour by delta 9-tetrahydrocannabinol.

    abstract::Rats chronically treated with increasing daily doses of delta 9-tetrahydrocannabinol (delta 9-THC) for up to 5 or 10 days exhibit a withdrawal-like behavioural response when challenged with clomipramine, a potent inhibitor of serotonin (5-hydroxytryptamine) reuptake, at the time when the next injection of delta 9-THC ...


    pub_type: 杂志文章


    authors: Verberne AJ,Taylor DA,Fennessy MR

    更新日期:1981-01-01 00:00:00

  • Tolerance to the anti-pentylenetetrazole effects of diazepam in the mouse.

    abstract::The protective effects of acute and chronic diazepam administration (4 mg/kg) against seizures induced by pentylenetetrazole (PTZ) and picrotoxin were investigated. Considering the incidence of tonic-clonic convulsions, tolerance to the protective effects of diazepam was evident by day 5 if the mice were challenged wi...


    pub_type: 杂志文章


    authors: File SE

    更新日期:1983-01-01 00:00:00

  • Tyramine infusions and selective monoamine oxidase inhibitor treatment. II. Interrelationships among pressor sensitivity changes, platelet MAO inhibition, and plasma MHPG reduction.

    abstract::The relationship between changes in IV tyramine pressor sensitivity accompanying selective monoamine oxidase (MAO) inhibitor treatment and estimates of MAO-A and MAO-B inhibition in vivo were studied. Reductions in platelet MAO activity provided an index of MAO-B inhibition, while changes in plasma 3-methoxy-4-hydroxy...


    pub_type: 杂志文章


    authors: Pickar D,Cohen RM,Jimerson DC,Lake CR,Murphy DL

    更新日期:1981-01-01 00:00:00

  • The contribution of α4β2 and non-α4β2 nicotinic acetylcholine receptors to the discriminative stimulus effects of nicotine and varenicline in mice.

    abstract:RATIONALE:The extent to which non-α4β2 versus α4β2* nAChRs contribute to the behavioral effects of varenicline and other nAChR agonists is unclear. OBJECTIVES:The purpose of this study was to characterize the discriminative stimulus effects of varenicline and nicotine using various nAChR agonists and antagonists to el...


    pub_type: 杂志文章


    authors: de Moura FB,McMahon LR

    更新日期:2017-03-01 00:00:00

  • Response sensitization and depression following long-term amphetamine treatment in a self-stimulation paradigm.

    abstract::The effects of long-term amphetamine treatment were evaluated on responding supported by self-stimulation of the substantia nigra. Rats repeatedly treated with d-amphetamine, and tested with a low dose of the drug that ordinarily has no behavioral effect, showed higher response rates than animals repeatedly treated wi...


    pub_type: 杂志文章


    authors: Kokkinidis L,Zacharko RM

    更新日期:1980-01-01 00:00:00

  • Disruption of prepulse inhibition of the startle reflex by the preferential D(3) agonist ropinirole in healthy males.

    abstract:RATIONALE:Emerging evidence from agonist-antagonist studies suggests a role for the dopamine D(3) receptor subtype in the regulation of PPI in animals, but such evidence is lacking for human subjects. OBJECTIVES:This study examines the effect of the preferential D(3) agonist ropinirole on PPI in humans. METHODS:PPI w...


    pub_type: 杂志文章


    authors: Giakoumaki SG,Roussos P,Frangou S,Bitsios P

    更新日期:2007-10-01 00:00:00

  • Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse.

    abstract:RATIONALE:Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed. OBJECTIVES:We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawa...


    pub_type: 杂志文章


    authors: Haney M,Hart CL,Vosburg SK,Comer SD,Reed SC,Cooper ZD,Foltin RW

    更新日期:2010-08-01 00:00:00

  • Beta receptor-mediated modulation of the late positive potential in humans.

    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...


    pub_type: 杂志文章,随机对照试验


    authors: de Rover M,Brown SB,Boot N,Hajcak G,van Noorden MS,van der Wee NJ,Nieuwenhuis S

    更新日期:2012-02-01 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 ...


    pub_type: 杂志文章


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

    更新日期:2020-03-01 00:00:00

  • Erythrocyte glycine in depressed, hypomanic, and euthymic bipolar patients treated with lithium carbonate.

    abstract::Red blood cell (RBC) glycine levels were examined in 27 bipolar patients, treated with lithium carbonate for a minimum of 8 months, who were either hypomanic, depressed, or euthymic in their mood. We found no difference in the RBC glycine or in the RBC: plasma glycine ratio between the hypomanic, depressed, or euthymi...


    pub_type: 杂志文章


    authors: Peselow ED,Deutsch SI,Stanley M,Banay-Schwartz M,Virgilio J,Fieve RR

    更新日期:1982-01-01 00:00:00

  • Chronic effects of ethosuximide, phenytoin, clonazepam, and valproic acid on the delayed-matching-to-sample performance of pigeons.

    abstract::Acute and chronic effects of ethosuximide (40, 80, and 120 mg/kg), phenytoin (2.5, 5, and 7.5 mg/kg), clonazepam (0.25, 0.5, and 0.75 mg/kg), and valproic acid (40, 80, and 120 mg/kg) were examined in pigeons performing under a delayed-matching-to-sample procedure. Acute administration of clonazepam or valproic acid p...


    pub_type: 杂志文章


    authors: Poling A,Picker M,Vande Polder D,Clark R

    更新日期:1986-01-01 00:00:00

  • A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.

    abstract:RATIONALE:Schizophrenia is a complex neuropsychiatric disorder characterized, in part, by impaired dopamine signaling. TAK-063 is a selective inhibitor of phosphodiesterase 10A, a key regulator of intracellular signaling pathways that is highly expressed in the striatum. OBJECTIVE:Safety, tolerability, and pharmacokin...


    pub_type: 杂志文章,随机对照试验


    authors: Tsai M,Chrones L,Xie J,Gevorkyan H,Macek TA

    更新日期:2016-10-01 00:00:00

  • Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity.

    abstract:RATIONALE:Cessation of daily caffeine consumption produces a withdrawal syndrome comprised of subjective symptoms and functional impairment. Few controlled studies have examined the physiological effects of caffeine withdrawal. OBJECTIVE:The present study examined the effect of caffeine withdrawal on cerebral blood fl...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Jones HE,Herning RI,Cadet JL,Griffiths RR

    更新日期:2000-01-01 00:00:00

  • Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients.

    abstract::We are performing a double-blind trial with inward psychiatric patients. The indication for our psychotropic or psychotherapeutic intervention is mainly severe depression (= major depressive disorders DSM III). For a 3-week trial course trazodone (400 mg daily), amitriptyline (150 mg/die) or placebo capsules were give...


    pub_type: 临床试验,杂志文章


    authors: Klieser E,Lehmann E

    更新日期:1988-01-01 00:00:00

  • Time-dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain.

    abstract:RATIONALE:Schizophrenia is a severe, persistent, and fairly common mental illness. Haloperidol is widely used and is effective against the symptoms of psychosis seen in schizophrenia. Chronic oral haloperidol administration decreased the number of astrocytes in the parietal cortex of macaque monkeys (Konopaske et al., ...


    pub_type: 杂志文章


    authors: Konopaske GT,Bolo NR,Basu AC,Renshaw PF,Coyle JT

    更新日期:2013-11-01 00:00:00

  • Amygdaloid zif268 participated in the D-cycloserine facilitation effect on the extinction of conditioned fear.

    abstract:RATIONALE:The involvement of glutamate in fear extinction is perhaps the most promising in terms of facilitating clinical interventions for posttraumatic stress disorder (PTSD). This study was aimed at elucidating the possible role of zif268 on the D-cycloserine (DCS) facilitation effect on extinction. OBJECTIVE:We in...


    pub_type: 杂志文章


    authors: Wu IT,Tang TH,Ko MC,Chiu CY,Lu KT

    更新日期:2015-10-01 00:00:00

  • Agonist efficacy, drug dependence, and medications development: preclinical evaluation of opioid, dopaminergic, and GABAA-ergic ligands.

    abstract:BACKGROUND:The general premise that receptor theory provides a useful framework for understanding the behavioral effects of psychoactive drugs has been a central tenet of behavioral pharmacology. OBJECTIVES:The purpose of this review is to reiterate this basic theme and, in particular, the proposition that current con...


    pub_type: 杂志文章,评审


    authors: Bergman J,France CP,Holtzman SG,Katz JL,Koek W,Stephens DN

    更新日期:2000-12-01 00:00:00

  • Insights into functional pharmacology of α₁ GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?

    abstract:RATIONALE:Synthesis of ligands inactive or with low activity at α₁ GABA(A) receptors has become the key concept for development of novel, more tolerable benzodiazepine (BZ)-like drugs. WYS8, a remarkably (105 times) α₁-subtype selective partial positive modulator, may serve as a pharmacological tool for refining the ro...


    pub_type: 杂志文章


    authors: Joksimović S,Varagic Z,Kovačević J,Van Linn M,Milić M,Rallapalli S,Timić T,Sieghart W,Cook JM,Savić MM

    更新日期:2013-11-01 00:00:00

  • Chronic low-dose haloperidol effects on self-stimulation rate-intensity functions.

    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...


    pub_type: 杂志文章


    authors: Lynch MR,Carey RJ

    更新日期:1990-01-01 00:00:00

  • Context, acute tolerance, and subjective response affect alcohol-impaired driving decisions.

    abstract:RATIONALE:Alcohol intoxication produces effects that can impair judgment and increase engagement in risky behaviors, including alcohol-impaired driving (AID). Real-world AID decisions are informed by contextual circumstances and judgments of associated risk. How individuals vary in their AID decision-making across cont...


    pub_type: 杂志文章


    authors: Motschman CA,Warner OM,Wycoff AM,Davis-Stober CP,McCarthy DM

    更新日期:2020-12-01 00:00:00

  • Psychopharmacologic treatment of pediatric major depressive disorder.

    abstract:RATIONALE:The role of pharmacotherapy in the treatment of major depressive disorder (MDD) in youth has received much attention in recent years due to concerns of efficacy and safety of the antidepressants for the treatment of MDD in youth. OBJECTIVES:This review describes the existing published and unpublished literat...


    pub_type: 杂志文章,评审


    authors: Boylan K,Romero S,Birmaher B

    更新日期:2007-03-01 00:00:00