The main theme of my laboratory concerns the neurochemical, neurotoxic, and behavioral effects of psychostimulant drugs. Our current research is focused on MDMA (also known as "Ecstasy"), a recreational drug that is widely used and sometimes abused by adolescents and young adults. MDMA is a potent releaser of the neurotransmitter serotonin, and it also stimulates dopamine and norepinephrine release. These effects are thought to underlie the complex psychological properties of MDMA in humans, which include arousal, euphoria, increased sensitivity to sensory stimuli, and enhanced sociality. In laboratory animals such as rats and monkeys, high doses of MDMA are thought to damage serotonergic fibers in many forebrain areas, including the neocortex, hippocampus, and striatum. This distal axotomy is accompanied by changes in emotionality, anxiety, and cognitive function in the treated animals. Neuropsychological and neuroimaging studies of heavy MDMA users suggest that humans may likewise be vulnerable to MDMA-induced serotonergic neurotoxicity; however, such a conclusion is still tentative at this time due to confounding experimental factors in many of these studies.
My laboratory is particularly interested in the consequences of MDMA exposure at different stages of development. For example, we have shown that treatment of newborn rat pups (a model of human drug exposure during the third trimester of pregnancy) with MDMA for just 4 days causes an immediate increase in apoptotic cell death in non-serotonergic neurons within the forebrain, as well as a long-term reorganization of the forebrain serotonergic innervation (Meyer et al., 2004, International Journal of Developmental Neuroscience).
Jerrold S. Meyer
Neurochemistry; Neuropharmacology;
Neurobehavioral Effects of Abused Drugs During
Development
Interestingly, this treatment paradigm also causes enhanced sensitivity
to an MDMA challenge given in adulthood (Piper and Meyer, in press, Neurotoxicology
and Teratology). Much of our current work is based on the fact that
users often begin taking MDMA during adolescence, and they commonly take
the drug on weekends at dances or other social events. Consequently, we
have developed a novel rat model of intermittent adolescent MDMA exposure
and have begun to investigate the neural and behavioral effects of such
exposure. Our first study demonstrated that rats given MDMA repeatedly during
adolescence showed a later reduction in anxiety-like behavior and a deficit
in working memory (Piper and Meyer, 2004, Pharmacology, Biochemistry
and Behavior). More recently, we showed that adolescent MDMA exposure
completely protects animals from the neurotoxic and behavioral effects of
a subsequent high dose of MDMA (Piper et al., submitted for publication).
Some of the current projects in the lab are aimed at following up these
findings by determining whether adolescent MDMA treatment alters the metabolism
of the drug or affects brain enzyme systems that would be expected to counteract
MDMA's neurotoxic actions. We are also interested in the influence of adolescent
MDMA exposure on the expression and sensitivity of serotonergic receptors,
particularly the 5-HT1A and 5-HT2A receptors.
To accomplish these aims, we use a variety of methodological approaches,
including behavioral tests (e.g., elevated plus-maze, object recognition
memory test, forced swim test, social interaction test), immunocytochemistry
for the serotonin transporter (to visualize serotonergic fibers) and for
immediate-early genes (to determine the effects of MDMA on signal transduction
mechanisms), radioligand binding (e.g., for serotonin receptor measurements),
Western blotting (e.g., for quantification of serotonin transporter protein
expression), and HPLC for measurement of plasma and brain MDMA and its bioactive
metabolite MDA.
