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Parametric Studies Of Antipsychotic-Induced Sensitization In The Conditioned Avoidance Response Model: Roles Of Number Of Drug Exposure, Drug Dose, And Test–Retest Interval, Natashia Swalve, Ming Li

Department of Psychology: Faculty Publications

Repeated haloperidol and olanzapine treatment produces an enhanced disruption of avoidance responding, a validated measure of antipsychotic activity. Experimental parameters affecting this sensitization-like effect have not been thoroughly examined. The present study investigated the role of three parameters (number of injections, dose, and interval between initial exposure and challenge) in antipsychotic sensitization in the conditioned avoidance response paradigm. Well-trained Sprague–Dawley rats received different numbers of drug treatment (1–5 days) or different doses of haloperidol (0.025–0.10 mg/kg, subcutaneously) or olanzapine (0.5–2.0 mg/kg, subcutaneously). After certain time intervals (4, 10 or 17 days), they were tested for the expression of haloperidol or …

Olanzapine And Risperidone Disrupt Conditioned Avoidance Responding In Phencyclidine-Pretreated Or Amphetamine-Pretreated Rats By Selectively Weakening Motivational Salience Of Conditioned Stimulus, Ming Li, Wei He, Alexa Mead

Ming Li

The rat conditioned avoidance response model is a well-established preclinical behavioral model predictive of antipsychotic efficacy. All clinically approved antipsychotic drugs disrupt conditioned avoidance responding – a feature that distinguishes them from other psychotherapeutics. We previously showed that the typical antipsychotic drug haloperidol disrupts avoidance responding by progressively attenuating the motivational salience of the conditioned stimulus (CS) in normal rats. In this study, using two pharmacological rat models of schizophrenia [e.g. phencyclidine (PCP) or amphetamine sensitization], we examined whether atypicals such as olanzapine or risperidone disrupt avoidance responding through the same behavioral mechanism. Rats were first pretreated with PCP, amphetamine, …

Clozapine, But Not Olanzapine, Disrupts Conditioned Avoidance Response In Rats By Antagonizing 5-Ht2a/2c Receptors, Ming Li, Tao Sun, Alexa Mead

Ming Li

The present study was designed to assess the role of 5-HT2A/2C receptors in the acute and repeated effect of clozapine and olanzapine in a rat conditioned avoidance response model, a validated model of antipsychotic activity. Male Sprague–Dawley rats that were previously treated with either phencyclidine (0.5–2.0 mg/kg, sc), amphetamine (1.25–5.0 mg/kg, sc), or saline and tested in a prepulse inhibition of acoustic startle study were used. They were first trained to acquire avoidance response to a white noise (CS1) and a pure tone (CS2) that differed in their ability to predict the occurrence of footshock. Those who acquired avoidance response …

Anxiolytic-Like Property Of Risperidone And Olanzapine As Examined In Multiple Measures Of Fear In Rats, Tao Sun, Wei He, Gang Hu, Ming Li

Ming Li

Atypical antipsychotics are also used in the treatment of anxiety-related disorders. Clinical and preclinical evidence regarding their intrinsic anxiolytic efficacy has been mixed. In this study, we examined the potential anxiolytic-like effects of risperidone and olanzapine, and compared them with haloperidol, chlordiazepoxide (a prototype of sedative–anxiolytic drug) or citalopram (a selective serotonin reuptake inhibitor). We used a composite of two-way avoidance conditioning and acoustic startle reflex model and examined the effects of drug treatments during the acquisition phase (Experiment 1) or extinction phase (Experiments 2 and 3) on multiple measures of conditioned and unconditioned fear/anxiety-like responses. In Experiment 4, we …

Interactions Between Antiepileptics And Second-Generation Antipsychotics, Jose De Leon, Vincenza Santoro, Concetta D'Arrigo, Edoardo Spina

Psychiatry Faculty Publications

INTRODUCTION: Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, particularly in bipolar disorder.

AREAS COVERED: This article provides a comprehensive review of the interactions between antiepileptics and second-generation antipsychotics. The authors cover pharmacokinetic AED-SGAP DI studies, the newest drug pharmacokinetics in addition to the limited pharmacodynamic DI studies.

EXPERT OPINION: Dosing correction factors and measuring SGAP levels can help to compensate for the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone. Further studies …

Is Asenapine More Effective Than Other Interventions In The Treatment Of Adult Patients With Bipolar I Disorder?, Mary H. Tsakiris

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Asenapine is more effective than other interventions in the treatment of adult patients with bipolar I disorder.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2009-2010.

DATA SOURCES: Three randomized controlled trials studying the effectiveness of Asenapine in the treatment of mania in adult patients with bipolar I disorder in comparison to other interventions.

OUTCOME MEASURED: Outcomes measured were reduction in severity of manic symptoms and tolerability of the medication. The severity of manic symptoms was measured using the Young …

Contextual And Behavioral Control Of Antipsychotic Sensitization Induced By Haloperidol And Olanzapine, Chen Zhang, Ming Li

Department of Psychology: Faculty Publications

Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic- induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model …

Clozapine, But Not Olanzapine, Disrupts Conditioned Avoidance Response In Rats By Antagonizing 5-Ht2a/2c Receptors, Ming Li, Tao Sun, Alexa Mead

Department of Psychology: Faculty Publications

The present study was designed to assess the role of 5-HT_2A/2C receptors in the acute and repeated effect of clozapine and olanzapine in a rat conditioned avoidance response model, a validated model of antipsychotic activity. Male Sprague–Dawley rats that were previously treated with either phencyclidine (0.5–2.0 mg/kg, sc), amphetamine (1.25–5.0 mg/kg, sc), or saline and tested in a prepulse inhibition of acoustic startle study were used. They were first trained to acquire avoidance response to a white noise (CS1) and a pure tone (CS2) that differed in their ability to predict the occurrence of footshock. Those who acquired avoidance …