Integrated in vivo pharmacology using an instrumented, unrestrained and conscious rat platform: application to rat models of diabetes.
BACKGROUND
We define the technical and methodological aspects that led to a practical and reproducible biological in vivo platform allowing the measurement of more than 65 physiobiochemical parameters on a daily basis in freely moving conscious animals. Such a platform presents the ability to unleash incremental information in the hands of modern-day pharmacologists and physiologists.


METHODS
To validate this platform, we fully characterized three rat models of Type 1 and Type 2 diabetes and their respective controls. Control, streptozotocin- and alloxan-diabetic Wistar rats in addition to ZDF-Lean and ZDF-Fatty rats were chronically implanted with an arterial catheter and kept in metabolic cages. The catheter was connected to a minipump infusing saline at a constant rate to maintain patency and used to collect blood and measure hemodynamic parameters on a daily basis.


RESULTS
Catheter implantation was successful in over 95% of animals and catheter patency was successfully maintained for 30 days in about 75% of animals. The three diabetic rat strains showed elevations in food and water consumption, urinary output, plasma glucose, blood urea nitrogen, triglycerides and cholesterol. The two Type I models also showed a depressed body weight and hemodynamic function. The STZ model differed from the alloxan-model by elevations in liver enzyme activities (AST, ALT, and bilirubin) and a more severe dyslipidemia (triglycerides and total cholesterol). The ZDF-Fatty rats distinguished themselves by higher body weight and elevated white blood cell counts.


CONCLUSIONS
This integrated platform represents a significant improvement in standard in vivo evaluations and could greatly improve the pace of development of potential new drugs.
Nantel
François
F
IPS Pharma, 3001 North, 12th avenue, Sherbrooke, QC, Canada J1H 5N4.
Daull
Philippe
P
Berthiaume
Nathalie
N
Duta
Dana-Nicoleta
DN
Blouin
André
A
Cayer
Julie
J
Beaudoin
Myriam
M
Belleville
Karine
K
Benrezzak
Ouhida
O
Sirois
Pierre
P
Battistini
Bruno
B
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003243:Consciousness; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000652:urine*; D003922:Diabetes Mellitus, Type 1; D003924:Diabetes Mellitus, Type 2; D004195:Disease Models, Animal; D004326:Drinking; D004435:Eating; D004573:Electrolytes / Q000097:blood / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007677:Kidney Function Tests; D008111:Liver Function Tests; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D015203:Reproducibility of Results; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D004573:Electrolytes; D014280:Triglycerides; D002784:Cholesterol