Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats

Shobo, Miwako; Yamada, Hiroshi; Koakutsu, Akiko; Hamada, Naoko; Fujii, Masahiro; Harada, Kensuke; Ni, Keni; Matsuoka, Naoki

doi:10.1016/j.lfs.2011.02.014

Cited by 19 publications

(18 citation statements)

References 30 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the majority of these acute and/or meal patterning studies use subtherapeutic doses of OLA based on D 2 occupancy, which is relevant as higher doses may be associated with drug-related sedation or motor side effects that could compromise evaluation of feeding behaviors (Fernø et al 2015;Shobo et al 2011a). Nonetheless, our review suggests that recording only cumulative food intake may miss changes in meal patterning and motivational factors influencing feeding.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Shobo et al (2011b) also fed male Sprague Daley rats ad libitum high carbohydrate/fat diet with OLA mixed into food (5-10 mg/kg/day) and found increases in food intake and weight (with the 5 mg/kg/day dose of OLA only) and fat pads (all doses of OLA versus controls). Conversely, when the same group looked at OLA administration via mini-pumps for 42 days (7.5 mg/kg/day) while providing a high carbohydrate/fat diet they noted increased adiposity but failed to replicate earlier findings of hyperphagia (Shobo et al 2011a). While no single AP drug has a defined therapeutic serum level, the study by Shobo reported OLA levels approximating~2000 nmol/L.…”

Section: Clozapinementioning

confidence: 92%

“…However, studies examining repeated/ chronic dosing paradigms of OLA show interesting sex differences. In general, regardless of route or frequency of OLA administration, chronically treated female rats or mice demonstrate increases in cumulative food intake and weight (Arjona et al 2004;Choi et al 2007;Cope et al 2005;Evers et al 2010;Fell et al 2004;Fell et al 2007;Kalinichev et al 2005;Mann et al 2013;Pouzet et al 2003;Snigdha et al 2008;Weston-Green et al 2011;Huang et al 2006), whereas findings in males generally fail to demonstrate an effect on food intake or weight gain (Choi et al 2007;Minet-Ringuet et al 2006a;Pouzet et al 2003;Shobo et al 2011a).…”

Section: Clozapinementioning

confidence: 94%

See 2 more Smart Citations

Atypical antipsychotics and effects on feeding: from mice to men

et al. 2016

View full text Add to dashboard Cite

The findings from this review indicate that the varying levels of AAP-related weight gain reflect changes in both appetite and feeding behaviors, which differ by type of AAP. However, inconsistencies exist among the studies (both human and rodent) that may reflect considerable differences in study design and methodology. Future studies examining underlying mechanisms of antipsychotic-induced weight gain are recommended in order to develop strategies addressing the serious metabolic side effect of AAPs.

show abstract

Section: Discussion/conclusionmentioning

confidence: 99%

Section: Clozapinementioning

confidence: 92%

Section: Clozapinementioning

confidence: 94%

See 1 more Smart Citation

Atypical antipsychotics and effects on feeding: from mice to men

et al. 2016

View full text Add to dashboard Cite

show abstract

“…As the number of daily administrations through injection or gavage is, for practical reasons, limited, and food/ water intake is unevenly distributed throughout the light/dark phases, all these approaches result in marked variation in serum concentrations during a 24 h period (Perez-Costas et al, 2008). In order to circumvent the problem of fluctuating drug serum concentrations, osmotic minipumps have been employed (Choi et al, 2007;Mann et al, 2013;Shobo et al, 2011). However, results are conflicting and minipumps have been characterized as a non-optimal mode of long-term administration of antipsychotics to rats (Remington et al, 2011;van der Zwaal et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Olanzapine depot formulation in rat: a step forward in modelling antipsychotic-induced metabolic adverse effects

Skrede

Martins

Berge

et al. 2013

Int. J. Neuropsychopharm.

View full text Add to dashboard Cite

Rats are used as animal models in the study of antipsychotic-induced metabolic adverse effects, with oral drug administration yielding hyperphagia, weight gain and, in some cases, lipogenic effects. However, the rapid half-life of these drugs in rats, in combination with development of drug tolerance after a few weeks of treatment, has limited the validity of the model. In order to prevent fluctuating drug serum concentrations seen with daily repeated administrations, we injected female rats with a single intramuscular dose of long-acting olanzapine formulation. The olanzapine depot injection yielded plasma olanzapine concentrations in the range of those achieved in patients, and induced changes in metabolic parameters similar to those previously observed with oral administration, including increased food intake, weight gain and elevated plasma triglycerides. Moreover, the sensitivity to olanzapine was maintained beyond the 2-3 wk of weight gain observed with oral administration. In a separate olanzapine depot experiment, we aimed to clarify the role of hypothalamic AMP-activated protein kinase (AMPK) in olanzapine-induced weight gain, which has been subject to debate. Adenovirus-mediated inhibition of AMPK was performed in the arcuate (ARC) or the ventromedial hypothalamic (VMH) nuclei in female rats, with subsequent injection of olanzapine depot solution. Inhibition of AMPK in the ARC, but not in the VMH, attenuated the weight-inducing effect of olanzapine, suggesting an important role for ARC-specific AMPK activation in mediating the orexigenic potential of olanzapine. Taken together, olanzapine depot formulation provides an improved mode of drug administration, preventing fluctuating plasma concentrations, reducing handling stress and opening up possibilities to perform complex mechanistic studies.

show abstract

“…Two types of implantable infusion pumps, iPRECIO ® SMP200 and Alzet TM 2ML4 (as representative osmotic infusion pump), were used for the iP-group and OSM-group, respectively (Abe et al, 2009;Joles et al, 1992;Sherratt et al, 1988;Ronis et al, 2001;Shobo et al, 2011;Tan et al, 2011;Turner et al, 2011). The iPRECIO ® pump (38.7 × 19.2 × 9.7 mm/7.9 g; reservoir volume, 0.9 mL; Fig.…”

Section: Infusion Pumps and Implantation Surgerymentioning

confidence: 99%

Physiological conditions in iPRECIO<sup>®</sup> -implanted rats

Tsuboi¹,

Ueda²,

Ota³

et al. 2016

Fundam. Toxicol. Sci.

View full text Add to dashboard Cite

-Any devices used in toxicity studies should be validated. In the present study, the physiological conditions of rats implanted with a new micro-infusion pump, iPRECIO ® , were examined to evaluate its availability for toxicity studies. Five or six animals/group of 6-week-old male CD(SD) rats received either sham surgery or the implantation surgery for either the iPRECIO ® (iP) pump or a standard osmotic infusion pump (OSM) under the back skin. This was followed by 4 weeks (experiment I) or 13 weeks (experiment II) of observation. During the observation period, the iP-and OSM-animals received a continuous infusion of 2.0 or 2.5 μL/hr of saline via the external jugular vein. In experiment I, standard hematologic and blood chemical parameters used in toxicity studies were measured at weeks 1, 2, and 4. The iP-animals showed no abnormal changes in any parameters at any point when compared with the OSM-/SHAM-animals. In experiment II (only iP-and SHAM-animals), necropsy and histopathological examination were performed at weeks 1, 2, 4, and 13. The histopathological examination revealed foreign material-induced inflammatory changes in the dorsal subcutaneous tissue (implantation site) of the iP-animals, including the infiltration of polymorphonuclear or mononuclear cells, edema, granulation and fibrous capsule formation. However, the abnormalities were limited to the implantation site. These results suggest that the implantation of iPRECIO ® exerted no significant impact on the physiological condition of the rats. Therefore, we concluded that iPRECIO ® is applicable for toxicity studies.

show abstract

Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats

Cited by 19 publications

References 30 publications

Atypical antipsychotics and effects on feeding: from mice to men

Atypical antipsychotics and effects on feeding: from mice to men

Olanzapine depot formulation in rat: a step forward in modelling antipsychotic-induced metabolic adverse effects

Physiological conditions in iPRECIO<sup>®</sup> -implanted rats

Contact Info

Product

Resources

About