Vorhees-Williams-Skelton Lab

  • Amphetamines during Pregnancy and Stress

    As of 2006 (the latest data available), 25 percent of pregnant women entering drug treatment reported methamphetamine as her primary drug of abuse. This is compared with 8 percent in 1994.

    These data underestimate the prevalence of this problem for several reasons: the majority of drug users (pregnant or otherwise) do not enter treatment, and the trend line shows that prevalence is rising. Yet little is known about how methamphetamine or related drugs, such as methylenedioxymethamphetamine (MDMA), or ecstasy, affect brain development and behavior.

    The lab investigates both the similarities and differences in how these drugs work and how they result in enduring learning and memory impairments and what treatments might be developed to ameliorate such deficits. To do this, we developed a second- and third-trimester-equivalent rat model.

    In this model, both drugs result in adult offspring having impaired learning and memory. Methamphetamine causes ACTH release from the anterior pituitary and corticosterone release from the adrenals, and 5-HT reductions during the drug exposure. Long-term methamphetamine use causes residual DA reductions, alters dopamine D1 receptor function and changes DA turnover.

    MDMA also causes corticosterone release, but to a lesser extent than methamphetamine. The drug causes larger 5-HT reductions than methamphetamine and alters long-term 5-HT levels and changes 5-HT1A receptors, whereas methamphetamine does not. MDMA has long-term effects on glutamatergic NMDA receptors and postsynaptic signaling molecules (PSD95, nNOS and CAPON) in the hippocampus.

    Originally, we believed methamphetamine did not alter NMDA receptors. However, we recently obtained new data that MA may also have effects on these receptors, and we are continuing to investigate. Therefore, these structurally related, but psychologically different, drugs show a complex pattern of differential and overlapping effects on the developing brain.