CHRONIC INTRAVENOUS MODEL FOR STUDIES OF DRUG (AB)USE IN THE PREGNANTAND 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 sui tability of animal models, however, has been constrained by the availa bility of an appropriate route of administration. The commonly employe d 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 inhala tion or IV injection. The present study provides a method for the rout ine use of an IV administration model in pregnant and/or group-housed rats. Prior to mating, young adult female Sprague-Dawley rats were ane sthetized (ketamine/xylazine) for catheterization. A sterile Intracath IV catheter (22 ga., Becton/Dickinson) with a Luer-lock injection cap (Medex) was cut to similar to 8 cm and used as a SC dorsally implante d port for chronic IV injections. The distal end of the catheter was i nserted into the jugular vein and threaded centrally. Catheter patency was maintained by daily flushing with 0.2 ml of heparinized saline. F ollowing 1 week of surgical recovery, the mean (median)number of estru s cycles to impregnation was 2.5(2). The mean (+/- SEM) duration of ca theter 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, GD 15-20 x 2/day) had no significant effect on dam weight gain, gestation length, litter size, sex ratio, or birth weights. In sum, a subcutane ously implanted port provides a procedure for the routine IV administr ation of drugs to pregnant and/or group-housed rats which avoids (a) t he use of anesthesia/surgery during pregnancy, (b) the stress (restrai nt and/or thermal dilation) associated with tail vein injection, (c) t he difficulties of mating and single housing associated with tethered TV catheters, and (d) in the case of cocaine, precludes the potential confounds of any drug-induced non-IV parenteral lesions.