Developmental immunotoxicity of cocaine and ethanol in postnatal Lewis rats.
The immunomodulatory effect of cocaine (COC), ethanol (EtOH) and their combination was investigated in the developing immune system of postnatal Lewis rats. To simulate the route of exposure during lactation, newborn rats were orally treated with either saline, 20 mg COC/kg, and 0.6 g EtOH/kg or the coadministration of COC and EtOH from day 1 to 21 of life. Rat pups were sacrificed thirty minutes following the last treatment. Total lymphocytes and spleen/body weight ratios were decreased in animals exposed to COC. These immunotoxic effects were not enhanced by the coadministration of EtOH. However, pups exposed to both drugs had significantly decreased levels of serum immunoglobulin M (IgM) when compared to saline-treated rats. Plasma and tissue distribution studies revealed that the combination treatment group had a higher COC content in the brain and spleen as well as an increase in the metabolites benzoylecognine (BE) and norcocaine (NC) in the spleen. Ethylcocaine (EC) formation was not demonstrated in this model.
Figliomeni
M L
ML
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
Turkall
R M
RM
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000378:metabolism / Q000633:toxicity*; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007107:Immune System / Q000187:drug effects* / Q000254:growth & development; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew
D007075:Immunoglobulin M; D000431:Ethanol; D003042:Cocaine