Aripiprazole (OPC-14597) fully substitutes for the 5-HT 1A receptor agonist LY293284 in the drug discrimination assay in rats

Marona‐Lewicka, Danuta; Nichols, David E.

doi:10.1007/s00213-003-1677-6

Cited by 24 publications

(18 citation statements)

References 52 publications

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“…Under the present PR schedule, there was decreased responding for saline in rats after the pretreatment of aripiprazole (1-10 mg/kg). Similarly, a modest rate-decreasing effect of aripiprazole (2.5-5 mg/kg) was observed on operant responding and locomotor activity in rats (Marona-Lewicka and Nichols, 2004;Schwabe and Koch, 2006;Feltenstein et al, 2006) although behavior-disrupting effect of aripiprazole appeared to depend on which kind of behaviors was analyzed (Li et al, 2005). Therefore, it is possible that a rate-decreasing effect of aripiprazole is associated with the data under a PR schedule.…”

Section: Discussionmentioning

confidence: 93%

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Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration

Wee

Wang

Woolverton

et al. 2007

Neuropsychopharmacol

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Aripiprazole is a dopamine (DA) D 2 receptor partial agonist, approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. DA receptor partial agonists have been previously assessed as potential therapeutic agents for cocaine dependence. The present experiment examined the effect of aripiprazole on methamphetamine self-administration in a rodent model of an increasing drug self-administration with prolonged session duration. Wistar rats were allowed to self-administer methamphetamine (0.05 mg/kg/injection, intravenously) in either 1-h (short access: ShA rats) or 6-h sessions (long access: LgA rats). After 15 sessions, the dose-response function of methamphetamine was determined under either a progressive-or a fixed-ratio schedule. Next, the effect of aripiprazole (0.3-10 mg/ kg, subcutaneuously (s.c.)) on the dose-response function was examined. LgA rats exhibited an increasing rate of methamphetamine selfadministration. Responding for methamphetamine by LgA rats was higher than that of ShA rats under both schedules. Pretreatment with aripiprazole shifted the dose-response function of methamphetamine to the right in both LgA and ShA rats. However, the effect of aripiprazole was greater in LgA than ShA rats. In in vitro receptor binding assay, no change in the level of D 2 DA receptors in the nucleus accumbens and the striatum was found in any group. The present data suggest increased sensitivity of the dopaminergic system to aripiprazole in LgA rats compared with ShA rats. However, mechanisms other than downregulation of D 2 DA receptors in the nucleus accumbens and the striatum may be responsible for the increased sensitivity of the dopaminergic function in LgA rats.

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Section: Discussionmentioning

confidence: 93%

“…In addition to its action at DA D 2 receptors, aripiprazole has high affinity at 5-HT 1A and 5-HT 2A receptors (Burris et al, 2002;Shapiro et al, 2003;Marona-Lewicka and Nichols, 2004). Therefore, it is possible that aripiprazole influenced methamphetamine self-administration via an interaction with 5-HT 1A and 5-HT 2A receptors.…”

Section: Discussionmentioning

confidence: 99%

Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration

Wee

Wang

Woolverton

et al. 2007

Neuropsychopharmacol

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“…Aripiprazole also targets serotonin receptors, 5-HT1a, 5-HT2a, and 5-HT2c as partial agonist and/or antagonist (Lawler et al 1999;Shapiro et al 2003;Marona-Lewicka and Nichols 2004;Kleven et al 2005;Auclair et al 2006;Stark et al 2007), and the serotonin system has also been implicated in mediating the psychostimulant effects of cocaine via actions at these receptors (Müller and Huston 2006;Müller et al 2007). Aripiprazole has approximately ten times lower affinity for 5-HT1a receptors than for D 2 receptors (DeLeon et al 2004).…”

Section: Discussionmentioning

confidence: 95%

Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice

et al. 2008

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“…Data from binding studies consistently indicate that aripiprazole has a high affinity for dopamine D 2 (15,49,54,80) and D 3 (15,54,80) receptors, a moderate affinity for D 4 receptors (54,60) and low affinity for D 1 Functionally, aripiprazole has demonstrated both agonist and antagonist properties at the D 2 receptor, which fits a partial agonist pharmacologic profile (2,50,55,66,87). While aripiprazole has high affinity for D 2 receptors, it has low intrinsic efficacy (15,89).…”

Section: Dopamine (Da) Receptor Activitymentioning

confidence: 98%

Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

2004

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Aripiprazole (Abilify ® ) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia. Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G-protein coupled receptors (GPCRs) [especially dopamine (D 2 ) and 5-HT 1A ] and antagonistic action at others (especially 5-HT 2A ). Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia. In short-term studies rapid onset of action (within one week) has been demonstrated. Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder. At recommended doses, aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and schizoaffective disorder. There is only limited information available on the use of aripiprazole in children and adolescents, and pilot data suggest that a revised dosing strategy, based on weight, is indicated in this population. In the long-term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time-to-relapse.Aripiprazole represents the first functionally selective atypical antipsychotic drug.

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Aripiprazole (OPC-14597) fully substitutes for the 5-HT 1A receptor agonist LY293284 in the drug discrimination assay in rats

Cited by 24 publications

References 52 publications

Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration

Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration

Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice

Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

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