Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat

Hartfield, Abegale W.; Moore, Nicholas; Clifton, Peter G.

doi:10.1007/s00213-002-1368-8

Cited by 70 publications

(56 citation statements)

References 32 publications

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“…For the analysis from the data of Allison et al (1999), we used their preferred estimate of weight gain over 10 weeks, although the estimate for quetiapine depended on a study with shorter duration (see Table 4, footnote a, ). The minimal effective dose for Intralipid hyperphagia was taken from the present data or from Hartfield et al (2003a). Agents that did not enhance intake were assigned a value of 0 and we then calculated a Pearson correlation coefficient.…”

Section: Discussionmentioning

confidence: 99%

“…The drinking cages and procedure are similar to that already described (Lee and Clifton, 1992;Hartfield et al, 2003a) in that the test cages are standard solid-bottomed cages having a stainless-steel drinking spout attached to one side wall. Intralipid emulsion was delivered from a reservoir to the spout by a peristaltic pump via polythene tubing.…”

Section: Intralipid Intake Experimentsmentioning

confidence: 99%

“…In a series of studies, Baptista and co-workers have reported that chronic sulpiride treatment increases food intake and body weight in female, but not male, rats (Parada et al, 1989) and risperidone produces a similar sex-linked weight gain . Kaur and Kulkarni (2002) tested the antipsychotic compounds chlorpromazine, haloperidol, clozapine, olanzapine, risperidone, and sulpiride in female mice and found that food intake was increased over a time period ranging from 30 min to 2-5 h. Previously, we have reported that male rats significantly increased their consumption of a fat emulsion (10% Intralipid) during a 30-min test session following acute treatment with the atypical antipsychotic compounds clozapine or olanzapine (Hartfield et al, 2003a). There is conflicting evidence concerning gender differences in antipsychotic-associated weight gain in humans.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Atypical Antipsychotic Drugs on Intralipid Intake and Cocaine-Induced Hyperactivity in Rats

Hartfield

Moore

Clifton

2005

Neuropsychopharmacol

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Clozapine and olanzapine have been shown to acutely stimulate consumption of a fat emulsion (Intralipid) by male Lister hooded rats. We initially investigated the extent of any sex difference in Intralipid hyperphagia associated with olanzapine treatment. We then examined the degree of Intralipid hyperphagia produced by a range of atypical antipsychotic drugs having different associations with human weight gain, and also determined their effects on cocaine-stimulated locomotor activity as a measure of functional dopamine antagonism in vivo. Olanzapine (0.1-1 mg/kg) stimulated Intralipid intake to an equal extent in male and female rats. Quetiapine (10 mg/kg) also stimulated Intralipid intake whereas ziprasidone (0.3-10 mg/kg) or risperidone (0.03-0.3 mg/kg) did not have this effect. All of the compounds, except quetiapine, reduced cocaine-stimulated locomotor activity but the relationship to the degree of Intralipid hyperphagia was variable. Since there was a positive relationship between Intralipid hyperphagia and the reported extent of human body weight gain, we conclude that Intralipid hyperphagia may have predictive value for this drug-associated side effect and is not related to the dopamine antagonist properties of these agents.

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Section: Discussionmentioning

confidence: 99%

Section: Intralipid Intake Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Atypical Antipsychotic Drugs on Intralipid Intake and Cocaine-Induced Hyperactivity in Rats

Hartfield

Moore

Clifton

2005

Neuropsychopharmacol

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“…Observational preclinical (Thornton-Jones et al, 2002;Ota et al, 2002;Hartfield et al, 2003a;Arjona et al, 2004;Cope et al, 2005) and clinical data suggest that one of the ways SGAs can lead to changes in the patterns of food intake is by increasing appetite (Figure 5b; Bromel et al, 1998;Briffa and Meehan, 1998;Eder et al, 2001;Basson et al, 2001;Kinon et al, 2005) and subsequent consumption of the previously preferred diet (Gothelf et al, 2002;Kane et al, 2004).…”

Section: Effects Of Sgas On Food Intakementioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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“…Olanzapine administered i.p. significantly increased 30-min meal size of a fat emulsion (Intralipid, 10% emulsion of fatty acids) in rats, 14 and olanzapine and risperidone administered i.p. increased the food intake (10% sucrose added to standard mouse pellets) in female mice for 4 h after injection.…”

Section: Introductionmentioning

confidence: 98%

Antipsychotic drug-induced weight gain: development of an animal model

et al. 2005

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OBJECTIVE: Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. METHODS: Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. RESULTS: After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. CONCLUSIONS: Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

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Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat

Cited by 70 publications

References 32 publications

Effects of Atypical Antipsychotic Drugs on Intralipid Intake and Cocaine-Induced Hyperactivity in Rats

Effects of Atypical Antipsychotic Drugs on Intralipid Intake and Cocaine-Induced Hyperactivity in Rats

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Antipsychotic drug-induced weight gain: development of an animal model

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