Medicine and Health Sciences Commons^™

Adult Response To Olanzapine Or Clozapine Treatment Is Altered By Adolescent Antipsychotic Exposure: A Preclinical Test In The Phencyclidine Hyperlocomotion Model, Qing Shu, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

This study examined how repeated olanzapine (OLZ) or clozapine (CLZ) treatment in adolescence alters sensitivity to the same drug in adulthood in the phencyclidine (PCP) hyperlocomotion model. Male adolescent Sprague-Dawley rats (postnatal day (P) 44–48) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10.0 or 20.0 mg/kg, sc) and tested in the PCP (3.2 mg/kg, sc)-induced hyperlocomotion model for five consecutive days. Then a challenge test with OLZ (0.5 mg/kg) or CLZ (5.0 mg/kg) was administered either during adolescence (~P 51) or after the rats matured into adults (~P 76 and 91). During adolescence, repeated …

Neuroanatomical Substrates Of The Disruptive Effect Of Olanzapine On Rat Maternal Behavior As Revealed By C-Fos Immunoreactivity, Changjiu Zhao, Ming Li

Department of Psychology: Faculty Publications

Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0 mg/kg, sc). Maternal behavior was tested 2 h later, after which rats were sacrificed and brain tissues were collected. …

Drug–Drug Conditioning Between Citalopram And Haloperidol Or Olanzapine In A Conditioned Avoidance Response Model: Implications For Polypharmacy In Schizophrenia, Nathan L. Sparkman, Ming Li

Department of Psychology: Faculty Publications

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. …

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 …

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 …

Time Course Of The Attenuation Effect Of Repeated Antipsychotic Treatment On Prepulse Inhibition Disruption Induced By Repeated Phencyclidine Treatment, Ming Li, Erik He, Nick Volf

Department of Psychology: Faculty Publications

Antagonism of prepulse inhibition (PPI) deficits produced by psychotomimetic drugs has been widely used as an effective tool for the study of the mechanisms of antipsychotic action and identifying potential antipsychotic drugs. Many studies have relied on the acute effect of a single administration of antipsychotics, whereas patients with schizophrenia are treated chronically with antipsychotic drugs. The clinical relevance of acute antipsychotic effect in this model is still an open question. In this study, we investigated the time course of repeated antipsychotic treatment on persistent PPI deficit induced by repeated phencyclidine (PCP) treatment. After a baseline test with saline, male …

Olanzapine And Risperidone Disrupt Conditioned Avoidance Responding By Selectively Weakening Motivational Salience Of Conditioned Stimulus: Further Evidence, Chen Zhang, Yiru Fang, Ming Li

Department of Psychology: Faculty Publications

Suppression of conditioned avoidance response is a preclinical behavioral index of antipsychotic activity. Previous work shows that olanzapine and risperidone disrupt avoidance response elicited by a less salient conditioned stimulus (CS2) to a greater extent than avoidance elicited by a more salient stimulus (CS1), suggesting that antipsychotic drugs may have a weakening action on motivational salience of stimuli. In the present study, we further examined this mechanism of antipsychotic action, focusing on the possible impact of baseline difference of CS1 and CS2 response rates on the avoidance-disruptive effect of olanzapine and risperidone. Rats were first trained to acquire avoidance responding …

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

Department of Psychology: Faculty Publications

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 …

Distinct Neural Mechanisms Underlying Acute And Repeated Administration Of Antipsychotic Drugs In Rat Avoidance Conditioning, Ming Li, Tao Sun, Chen Zhang, Gang Hu

Department of Psychology: Faculty Publications

Rationale — Acute antipsychotic treatment disrupts conditioned avoidance responding, and repeated treatment induces a sensitization- or tolerance-like effect. However, the neurochemical mechanisms underlying both acute and repeated antipsychotic effects remain to be determined.

Objective — The present study examined the neuroreceptor mechanisms of haloperidol, clozapine, and olanzapine effect in a rat two-way conditioned avoidance model.

Methods — Well-trained Sprague–Dawley rats were administered with haloperidol (0.05 mg/kg, sc), clozapine (10.0 mg/ kg, sc), or olanzapine (1.0 mg/kg, sc) together with either saline, quinpirole (a selective dopamine D2/3 agonist, 1.0 mg/ kg, sc), or 2,5-dimethoxy-4-iodo-amphetamine (DOI; a selective 5-HT2A/2C agonist, 2.5 mg/kg, …

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

Department of Psychology: Faculty Publications

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, …