Cf. Mactutus et al., CHRONIC INTRAVENOUS MODEL FOR STUDIES OF DRUG (AB)USE IN THE PREGNANTAND OR GROUP-HOUSED RAT - AN INITIAL STUDY WITH COCAINE/, Neurotoxicology and teratology, 16(2), 1994, pp. 183-191
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.