|Jerrold S. Meyer
Professor of Psychology, University of Massachusetts
Ph.D.: University of Wisconsin
Neurotransmitter Development and its Modulation by Psychoactive Drugs
We are interested in the development of the monoaminergic neurotransmitter systems (i.e., dopamine, DA; serotonin, 5-HT; and norepinephrine, NE) and how these systems are influenced by early exposure to drugs of abuse or compounds used in the treatment of psychopathological disorders. Much of our recent work has involved the use of a rat model to determine the mechanisms of cocaine action on the developing brain and the neurochemical and behavioral consequences of chronic prenatal cocaine exposure. Previous studies had shown that cocaine binds to the plasma membrane transporters for DA, NE, and 5-HT, thereby blocking the synaptic reuptake of these transmitters and potentiating their activity. We have determined the pharmacological characteristics and distribution of these transporters in fetal and adult brain using several radioligands, including the cocaine analog [125I]RTI-55 (which binds to both DA and 5-HT transporters) as well as other drugs that more selectively label individual transporter subtypes.
Another possible target of developmental cocaine action is the placenta, which expresses both transporters and receptors for NE and 5-HT. We have investigated the normal distribution of placental transporters using in vitro autoradiography, and we have also shown that maternal cocaine treatment up-regulates the placental NE transporter and may down-regulate the ß-adrenergic receptor system. Current lab projects include the effects of prenatal cocaine treatment on signal transduction mechanisms and modulation of DA-regulated neuropeptide gene expression in the brain.
Tiefenbacher, S., Novak, M. A., Lutz, C. C., & Meyer, J. S. The physiology and neurochemistry of self-injurious behavior: a nonhuman primate model. Frontiers in Bioscience 10: 1-11 (2005) (invited review article for special issue on Primate Models of Psychopathology).
Piper, B. J., & Meyer, J. S. Increased responsiveness to MDMA in adult rats treated neonatally with MDMA. Neurotoxicology and Teratology in press (2005).
Piper, B. J., Fraiman, J. B., & Meyer, J. S. Repeated MDMA ("Ecstasy") exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention, and serotonin transporter levels. Developmental Psychobiology 47: 145-157 (2005).
Tiefenbacher, S., Fahey, M. A., Rowlett, J. K., Meyer, J. S., Pouliot, A. L, Jones, B. M., and Novak, M. A. The efficacy of diazepam treatment for the management of acute wounding episodes in captive rhesus macaques. Comparative Medicine 55: 387-392 (2005).
Tiefenbacher, S., Novak, M. A., Marinus, L. M., Chase, W. K., Miller, J. A., & Meyer, J. S. Altered hypothalamic-pituitary-adrenocortical function in rhesus monkeys (Macaca mulatta) with self-injurious behavior. Psychoneuroendocrinology 29: 501-515 (2004).
Lutz, C., Tiefenbacher, S., Meyer, J., & Novak, M. Extinction deficits in male rhesus monkeys with a history of self-injurious behavior. American Journal of Primatology 63: 41-48 (2004).
Meyer, J. S., Grande, M., Johnson, K., & Ali, S. F. Neurotoxic effects of MDMA ("Ecstasy") administration to neonatal rats. International Journal of Developmental Neuroscience 22: 261-271 (2004) (invited paper for special issue on Developmental Aspects of Addiction).
Piper, B. J., & Meyer, J. S. Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period. Pharmacology, Biochemistry and Behavio r 79: 723-731 (2004).
Meyer, J. S., & Quenzer, L. F. Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates: Sunderland, MA, (2004) (textbook).
Lutz, C., Marinus, L., Chase, W., Meyer, J., & Novak, M. Self-injurious behavior in male rhesus macaques does not reflect externally-directed aggression. Physiology and Behavior 78: 33-39 (2003).
Tiefenbacher, S., Davenport, M. D., Novak, M. A., Pouliot, A. L., & Meyer, J. S. Fenfluramine challenge, self-injurious behavior, and aggression in rhesus monkeys. Physiology and Behavior 80: 327-331 (2003).
Meyer, J.S. Behavioral assessment in developmental neurotoxicology: Approaches involving unconditioned behaviors and pharmacological challenges in rodents. In: Handbook of Developmental Neurotoxicology, (W. Slikker and L.W. Chang, eds.), in press.
Brunzell, D. H., A. E. Coy, J. J. Ayres and J. S. Meyer (2002). "Prenatal cocaine effects on fear conditioning: Exaggeration of sex-dependent context extinction." Neurotoxicol Teratol 24(2): 161-72.
Meyer, J. S., I. Shani and D. Rice (2000). "Effects of neonatal cocaine treatment and gender on opioid agonist-stimulated [(35)S]GTP gamma S binding in the striatum and nucleus accumbens." Brain Res Bull 53(2): 147-52.
Meyer, J. S., T. A. Slotkin, N. E. Buckley and R. Sircar (2000). "Receptors for abused drugs: development and plasticity." Neurotoxicol Teratol 22(6): 773-84.
Meyer, J. S. and R. Kunkle (1999). "Behavioral responses to a D1 dopamine agonist in weanling rats treated neonatally with cocaine and delta9-tetrahydrocannabinol." Neurotoxicol Teratol 21(4): 375-80.
Collins, L.M., Pahl, J. and Meyer, J.S. (1999) Distribution of cocaine and metabolites in the pregnant rat and fetus in a chronic subcutaneous injection model. Neurotoxicol. Teratol. 21, 639-646.
Shearman, L.P. and Meyer, J.S. (1999) Cocaine up-regulates norepinephrine transporter binding in the rat placenta. Eur. J. Pharmacol. (in press).
McReynolds, A.M. and Meyer, J.S. (1998) Effects of prenatal cocaine exposure on serotonin and norepinephrine transporter density in the rat brain. Ann. N. Y. Acad. Sci. 846, 412-414.
Shearman, L.P., McReynolds, A.M., Zhou, F.C. and Meyer, J.S. (1998) Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta. Am. J. Physiol. 275, C1621-C1629.
Shearman, L.S. and Meyer, J.S. (1998) Monoamine transporters in rat placenta labeled with [3H]nisoxetine. J. Pharmacol. Exp. Ther. 284, 736-743.