Medicine and Health Sciences Commons^™

Effects Of Olanzapine And Betahistine Co-Treatment On Serotonin Transporter, 5-Ht2a And Dopamine D2 Receptor Binding Density, Jiamei Lian, Xu-Feng Huang, Nagesh Pai, Chao Deng

Xu-Feng Huang

Olanzapine is widely used in treating multiple domains of schizophrenia symptoms but induces serious metabolic side-effects. Recent evidence has showed that co-treatment of betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for preventing olanzapine-induced weight gain/obesity, however it is not clear whether this co-treatment affects on the primary therapeutic receptor binding sites of olanzapine such as serotonergic 5-HT2A receptors (5-HT2AR) and dopaminergic D2 receptors (D2R). Therefore, this study investigated the effects of this co-treatment on 5-HT2AR, 5-HT transporter (5-HTT) and D2R bindings in various brain regions involved in antipsychotic efficacy. Female Sprague Dawley rats were administered …

Effects Of Olanzapine On The Elevation Of Macrophage Infiltration And Pro-Inflammatory Cytokine Expression In Female Rats, Qingsheng Zhang, Meng He, Chao Deng, Hongqin Wang, Xu-Feng Huang

Xu-Feng Huang

The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage …

Differential Effects Of Short- And Long-Term Antipsychotic Treatment On The Expression Of Neuregulin-1 And Erbb4 Receptors In The Rat Brain, Chao Deng, Bo Pan, Chang-Hua Hu, Mei Han, Xu-Feng Huang

Xu-Feng Huang

Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short- or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70 kDa …

Chronic Betahistine Co-Treatment Reverses Olanzapine's Effects On Dopamine D2 But Not 5-Ht2a/2c Bindings In Rat Brains, Jiamei Lian, Xu-Feng Huang, Nagesh B. Pai, Chao Deng

Xu-Feng Huang

Olanzapine is widely prescribed for treating schizophrenia and other mental disorders, although it leads to severe body weight gain/obesity. Chronic co-treatment with betahistine has been found to significantly decrease olanzapine-induced weight gain; however, it is not clear whether this co-treatment affects the therapeutic effects of olanzapine. This study investigated the effects of chronic treatment of olanzapine and/or betahistine on the binding density of the serotonergic 5-HT2A (5-HT2AR) and 5-HT2C (5-HT2CR) receptors, 5-HT transporter (5-HTT), and dopaminergic D2 receptors (D2R) in the brain regions involved in antipsychotic efficacy, including the prefrontal cortex (PFC), cingulate cortex (Cg), nucleus accumbens (NAc), and caudate …

Olanzapine Treatment And Time-Dependent Changes Of Hypothalamic Ampk-Acc-Cpt1 Signalling, Food Intake And Body Weight In Rats, Meng He, Q Zhang, H Wang, Jiamei Lian, C Deng, Xu-Feng Huang

Xu-Feng Huang

No abstract provided.

Time-Dependant Alterations Of Hypothalamic Energy Regulatory Network By Olanzapine In Rats, Q Zhang, M He, Hongqin Wang, J Lian, C Deng, Xu-Feng Huang

Xu-Feng Huang

Abstract of a paper that presented at the Australian Neuroscience Society 32nd Annual meeting.

Novel Olanzapine Analogues Presenting A Reduced H1 Receptor Affinity And Retained 5ht2a/D2 Binding Affinity Ratio, Somayeh Jafari, Marc E. Bouillon, Xu-Feng Huang, Stephen G. Pyne, Francesca Fernandez-Enright

Xu-Feng Huang

Background Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios. Results We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors. Conclusions …

Reducing Olanzapine-Induced Weight Gain Side-Effect By Using Betahistine: A Study In The Rat Model, Chao Deng, Jiamei Lian, Nagesh Brahmavar Pai, Xu-Feng Huang

Xu-Feng Huang

Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug’s antagonistic affinity to histamine H1 receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H1 receptor agonist and H3 receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of …

Preventing And Treating Olanzapine-Induced Obesity With Betahistine: A Chronic Animal Model Study, Jiamei Lian, Xu-Feng Huang, Nagesh Pai, Chao Deng

Xu-Feng Huang

Objective : Olanzapine, an atypical antipsychotic drug, is widely prescribed to treat schizophrenia, but induces serious weight gain/ obesity side-effects. Antipsychotic drugs antagonistic affinity for histamine H1 receptors is the main indicator of weight gain side-effects. This study aimed to investigate whether chronic treatment with betahistine (H1 receptor agonist/H3 receptor antagonist) could prevent/ treat olanzapine-induced weight gain at different stages of treatment.

Methods : Female Sprague-Dawley rats were administered under 5 conditions (n=12) : (1) Rats were treated with vehicle (control) during whole experimental period ; (2) ‘‘Obesity treatment group’’ : 5 weeks olanzapine treatment (1 mg/kg, t.i.d.), followed by …

Histamine H1 Receptor Agonist And Control Of Olanzapine-Induced Obesity, Jiamei Lian, Xu-Feng Huang, N Pai, C Deng

Xu-Feng Huang

No abstract provided.

The Effects Of Antipsychotics On The Density Of Cannabinoid Receptors In The Dorsal Vagal Complex Of Rats: Implications For Olanzapine-Induced Weight Gain, Katrina Weston-Green, Xu-Feng Huang, Mei Han, Chao Deng

Xu-Feng Huang

Some atypical antipsychotics clinically used to treat schizophrenia induce weight gain by unknown mechanisms. The dorsal vagal complex (DVC) of the brainstem and the endogenous cannabinoid system are implicated in the regulation of appetite signalling and food intake. We investigated whether antipsychotic drugs alter cannabinoid receptor-binding density in the DVC. Female Sprague–Dawley rats were treated with olanzapine, haloperidol, aripiprazole or vehicle for 1 wk (short-term) or 12 wk (chronic). Quantitative autoradiographic methods were employed to investigate the binding density of cannabinoid receptors in the DVC using a highly sensitive Beta Imager. Short-term olanzapine induced a significant 39% decrease in cannabinoid …

Neuropeptide Y Mrna Expression Levels Following Chronic Olanzapine, Clozapine And Haloperidol Administration In Rats, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng

Xu-Feng Huang

No abstract provided.

Effects Of Chronic Treatment Of Olanzapine And Haloperidol On Peptide Yy Binding Densities In The Rat Brain, Xu-Feng Huang, Qing Wang

Xu-Feng Huang

This study examined regional changes of peptide YY (PYY) binding densities in the rat brain after chronic administration of olanzapine (1.2 mg/kg/day and haloperidol (2.0 mg/kg/day)for 36 days. PYY binding densities and distributions were detected by [125I] binding autoradiography after ratswere sacrificed either 2 h or 48 h after the last drug administration to examine both immediate and delayed effects following the drugwithdrawal. Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52 percent, pb0.05), dorsal part of medial geniculate nucleus (56 percent, pb0.05), …

Alterations To Melanocortinergic, Gabaergic And Cannabinoid Neurotransmission Associated With Olanzapine-Induced Weight Gain, Katrina Weston-Green, Xu-Feng Huang, Chao Deng

Xu-Feng Huang

Background/Aim: Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/ metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapineinduced obesity. Methodology/Results: Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD65, enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [3H]SR- 141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 …

Olanzapine Differentially Affects 5-Ht2a And 2c Receptor Mrna Expression In The Rat Brain, Xinyi Huang, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng, Mei Han

Xu-Feng Huang

No abstract provided.

Effects Of Olanzapine On Muscarinic M3 Receptor Binding Density In The Brain Relates To Weight Gain, Plasma Insulin And Metabolic Hormone Levels, Katrina Weston-Green, Xu-Feng Huang, Jiamei Lian, Chao Deng

Xu-Feng Huang

The second generation antipsychotic drug (SGA) olanzapine has an efficacy to treat schizophrenia, but can cause obesity and type II diabetes mellitus. Cholinergic muscarinic M3 receptors (M3R) are expressed on pancreatic β-cells and in the brain where they influence insulin secretion and may regulate other metabolic hormones via vagal innervation of the gastrointestinal tract. Olanzapine's M3R antagonism is an important risk factor for its diabetogenic liability. However, the effects of olanzapine on central M3Rs are unknown. Rats were treated with 0.25, 0.5, 1.0 or 2.0 mg olanzapine/kg or vehicle (3×/day, 14-days). M3R binding densities in the hypothalamic arcuate (Arc) and …