Medicine and Health Sciences Commons^™

Iptakalim: A Potential Antipsychotic Drug With Novel Mechanisms?, Tao Sun, Changjiu Zhao, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

Iptakalim is a novel putative adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channel opener. In the brain, iptakalim is thought to act on the neuronal and astrocytic plasma membrane and/or mitochondrial K_ATP channels. Because iptakalim demonstrates an action on the regulation of dopamine and glutamate release in the forebrain regions, we examined its potential antipsychotic efficacy in several preclinical tests. First, we show that iptakalim is effective in reducing amphetamine- and phencyclidine-induced hyperlocomotion as well as selectively disrupting conditioned avoidance responding. Next, we show that combined iptakalim and amphetamine treatment produces a reduction on prepulse inhibition of acoustic startle …

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, …