Prenatal cocaine exposure initiates the release of TIMP‐1 and MMP‐9 in primary neuronal and glial cell cultures (651.21)

Abstract

Drug addiction is a complex phenomenon that is mediated by biochemical events sequential to repeated exposure to a drug. The mechanisms underlying drug addiction include processes similar to those operating in forms of synaptic plasticity. Recently, pro‐addicitve cytokines, tissue inhibitors of matrix metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity consequent to repeated cocaine injections in animal models. The present study was designed to investigate the role of TIMP‐1 and MMP‐9 in the addiction neurobiology of offspring exposed to cocaine during gestation. Time pregnant Sprague‐Dawley rats were treated with 40 mg/kg of cocaine HCl on gestational day (GD) 10‐21. On postnatal day (PND) 2, the brain tissue of the pups was harvested to yield mixed primary neuronal and glial cell cultures. Primary cell cultures were also exposed to a second sub‐lethal dose of cocaine in vitro and their response was measured. An increase in TIMP‐1 and MMP‐9 expression was observed in prenatally exposed primary neuronal and glial cell cultures. Through in vivo and in vitro studies, these findings suggest that exposure to cocaine in utero initiates the release of pro‐addictive cytokines increasing the incidence of addiction in the affected offspring.Grant Funding Source: NIH‐NIMHD G12MD007582