Developmental effects of 3,4-methylenedioxymethamphetamine: a review

Abstract

Abstract± 3,4-Methylenedioxymethamphetamine (MDMA) is a chemical derivative of amphetamine that has become a popular drug of abuse and has been shown to deplete serotonin in the brains of users and animals exposed to it. To date, most studies have investigated the effects of MDMA on adult animals. With a majority of users of MDMA being young adults, the chances of the users becoming pregnant and exposing the fetuses to MDMA are also a concern. Evidence to date has shown that developmental exposure to MDMA results in learning and memory impairments in the Morris water maze, a task known to be sensitive to hippocampal disruption, when the animals are tested as adults. Developmental MDMA exposure leads to hypoactivity in the offspring as adults but does not affect outcome on tests of anxiety. MDMA administration decreases pup weight, increases corticosterone and brain-derived neurotrophic factor levels during treatment while decreasing brain levels of serotonin; a decrease that initially dissipates and then reappears in adulthood. Neonatal MDMA exposure increases the sensitivity of the serotonin 1A receptor, a possible mechanism underlying the learning and memory deficits seen. Taken together, the evidence shows that MDMA exposure has adverse effects on the developing brain and behavior. The animal and human data on developmental MDMA exposure are reviewed and their public health implications discussed.

Maternal MDMA administration in mice leads to neonatal growth delay

“…MDMA inhibits TH activity, resulting in impaired and damaged dopamine neurons and degeneration of serotonergic nerve terminals in adult animals (Battaglia et al, 1987;Schmidt and Taylor, 1987;O'Shea et al, 1998). Exposure of the fetus or newborn pup to MDMA does not cause such nerve toxicities (Skelton et al, 2008). The nervous system of infants is underdeveloped, and MDMA could be less toxic to these neurons.…”

One-Year Outcomes of Prenatal Exposure to MDMA and Other Recreational Drugs

“…27 MDMA treatment in animals correspondent to human prenatal exposure has been shown to disrupt the serotonergic system and induces the release of the stress hormone cortisol. 7 Many aspects of motor control have a serotonergic input, and serotonin may be more implicated in gross skeletal rather than fine or discrete muscle movements. 28 At 12 months, the Bayley Mental Scale items also have a strong motor component, as language…”

“…6 Preclinical studies indicate that prenatal MDMA exposure may induce behavioral alterations of long-term memory and learning impairments and increased locomotor activity. [7][8][9] First-trimester exposure has been related to reduced birth weight, increased locomotor activity, and learning deficits, 9 as well as long-term behavioral alternations of reduced anxiety, heightened response to novelty, and hyperattentiveness during spatial learning. 10 Recent studies indicate structural and functional changes in the noradrenergic system related to attention.…”

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

“…Given the widespread recreational use of MDMA (Ecstasy), pregnant women should be cautioned about possible developmental effects in offspring. Animal models need to be designed to include relevant doses and human developmental periods to best ascertain the developmental effects of MDMA (for an excellent review, see Skelton et al (2008)). …”