As of 2006, 25 percent of pregnant women entering drug treatment reported methamphetamine as their primary drug of abuse. This is compared with 8 percent in 1994. This upward trend has continued.

These data underestimate the prevalence of this problem since the majority of drug users do not enter treatment, and methamphetamine has become more widely available since 2006. Yet little is known about how methamphetamine affects brain development.

We investigate how methamphetamine affects brain development. We have found that it results in enduring learning and memory impairments. We are also interested in treatments that may ameliorate such deficits.

In our experiments, laboratory rats are exposed to methamphetamine during selected stages of brain development. We have found that early exposure to methamphetamine causes ACTH release from the anterior pituitary and corticosterone release from the adrenals, and transient reductions in brain serotonin (5-HT). After exposure ends, methamphetamine-exposed rats show long-term dopamine reductions, and altered dopamine D1 receptor function and utilization.

Developmental methamphetamine exposure also causes changes to dopamine D1, D2, and NMDA receptors. We are testing several hypotheses about the mechanisms of methamphetamine’s effects on brain development, including whether the drug induces reactive oxygen species (ROS) that may damage neurons or cause overstimulation of dopamine receptors. We are measuring markers of ROS and using microPET imaging to assess the functional integrity of dopamine-rich areas of the brain.

In adults, chronic methamphetamine users exhibit evidence of neurotoxicity by brain imaging, changes that can be replicated in laboratory rats. People who exhibit evidence of reduced brain dopamine uptake have impairments in learning and memory. How the drug causes cognitive effects is unknown. We are testing whether cognitive deficits can be prevented by injecting dopamine D1 and D2 receptor inhibitors into brain areas we hypothesize are critical to the cognitive deficits before exposing them to methamphetamine in order to test if these drugs are protective. These are proof of principle experiments that could lead to treatments to prevent the cognitive impairments if our hypothesis turns out to be true.