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Immunomodulation by cocaine and ketamine in postnatal rats
Hany Z Rofael1, Rita M Turkall, Mohamed S Abdel-Rahman
1Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Room I-655, Newark, NJ 07103-2714, USA.
Toxicology
|May 16, 2003
Summary
Cocaine exposure in newborn rats altered immune responses, increasing spleen weight and antibody production. Ketamine prevented these cocaine-induced effects, suggesting a neuroendocrine mechanism.
Area of Science:
- Toxicology
- Immunology
- Neuroendocrinology
Background:
- Substance abuse during pregnancy, particularly cocaine (COC) and ketamine (KET), poses risks to newborns via transplacental transfer and breast milk.
- Chronic cocaine exposure is known to modulate the immune system in both human and animal models.
- The impact of combined COC and KET exposure on the developing immune system requires further investigation.
Purpose of the Study:
- To assess the effects of sub-chronic exposure to cocaine (COC) and ketamine (KET), alone and in combination, on the developing immune system of neonatal rats.
- To investigate the potential role of neuroendocrine mechanisms in COC-induced immunomodulation and its prevention by KET.
Main Methods:
- Neonatal male Sprague-Dawley rats were orally administered saline, COC (20 mg/kg), KET (50 mg/kg), or KET followed by COC from day 1 to 21 of life.
- Measurements included total leukocyte and lymphocyte counts, spleen/body weight ratio, IgM antibody response to sheep red blood cells (SRBCs), serum IL-10 and IFN-gamma levels, and serum corticosterone concentration.
- Plasma and tissue concentrations of norcocaine (NC) were analyzed to assess the role of COC metabolism.
Main Results:
- COC exposure decreased leukocyte and lymphocyte counts, increased spleen/body weight ratio, and enhanced IgM response to SRBCs.
- COC alone increased serum IL-10 but not IFN-gamma. KET alone had no significant effects.
- Co-administration of KET with COC prevented COC-induced immunomodulatory effects and the increase in serum corticosterone.
Conclusions:
- Cocaine exposure induces significant immunomodulatory changes in neonatal rats, potentially mediated by neuroendocrine pathways.
- Ketamine co-administration effectively prevents cocaine-induced immunomodulation and corticosterone elevation.
- These findings suggest that neuroendocrine mechanisms play a crucial role in the interaction between cocaine and ketamine on the developing immune system.