Chronic intravenous model for studies of drug (Ab)use in the pregnant and/or group-housed rat: an initial study with cocaine.
Animal models for studying the developmental effects of maternal drug abuse are often based on chronic exposure of the pregnant rat. The suitability of animal models, however, has been constrained by the availability of an appropriate route of administration. The commonly employed SC and PO routes of administration fail to mimic the rapidly peaking pharmacokinetic profile observed in humans with licit (e.g., nicotine) and illicit (e.g., cocaine, methamphetamine) drugs abused via inhalation or i.v. injection. The present study provides a method for the routine use of an i.v. administration model in pregnant and/or group-housed rats. Prior to mating, young adult female Sprague-Dawley rats were anesthetized (ketamine/xylazine) for catheterization. A sterile Intracath i.v. catheter (22 ga., Becton/Dickinson) with a Luer-lock injection cap (Medex) was cut to approximately 8 cm and used as a SC dorsally implanted port for chronic i.v. injections. The distal end of the catheter was inserted into the jugular vein and threaded centrally. Catheter patency was maintained by daily flushing with 0.2 ml of heparinized saline. Following 1 week of surgical recovery, the mean (median)number of estrus cycles to impregnation was 2.5(2). The mean (+/- SEM) duration of catheter patency was 36.6 +/- 1.2 days and was in excess of 30 days for all animals (n = 22). Cocaine at a dose of 3 mg/kg (GD8-14 x 1/day, GD15-20 x 2/day) had no significant effect on dam weight gain, gestation length, litter size, sex ratio, or birth weight. In sum, a subcutaneously implanted port provides a procedure for the routine i.v. administration of drugs to pregnant and/or group-housed rats which avoids (a) the use of anesthesia/surgery during pregnancy, (b) the stress (restraint and/or thermal dilation) associated with tail vein injection, (c) the difficulties of mating and single housing associated with tethered i.v. catheters, and (d) in the case of cocaine, precludes the potential confounds of any drug-induced non-i.v. parenteral lesions.
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Division of Pharmacology & Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40546-0236.
Herman
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D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004777:Environment; D004971:Estrus / Q000187:drug effects; D005260:Female; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012744:Sex Ratio; D015819:Substance Abuse, Intravenous / Q000503:physiopathology*; D015430:Weight Gain / Q000187:drug effects
D003042:Cocaine