Pharmacology and Neuroscience
Dr. Arthur S. Freeman
Associate Professor of Pharmacology
Ph.D., 1982, Virginia Commonwealth University
Electrophysiological and Neurochemical Pharmacology of Midbrain Dopaminergic Neurons
Several neurological and psychiatric disorders are associated with altered function of midbrain dopamine (DA)-containing neurons. Treatment of DA-linked disorders with DA agonists or antagonists, however, is not always effective and is accompanied by undesirable side-effects. A great deal of basic research has focused on the autoregulatory role of DA on DA cell function. Continued investigation into the regulation of these neurons may ultimately yield alternative strategies to pharmacologically manipulate their function for therapeutic benefit.
Studies in our laboratory evaluate the effects of chronic administration of antipsychotic drugs on DA cell electrophysiology in rats. In particular, these studies assess the effects of promising antipsychotic drug candidates in comparison to benchmark compounds. The profile of effects for each drug often gives an indication if it will have therapeutic efficacy and if it is likely to produce motor side-effects in humans. Current studies also involve testing the hypothesis that diet may influence the responses of DA neurons to drug administration. This has clincial implications, such as predicting variable responses of patients with eating disorders to dopaminergic drugs.
Representative Publications
Freeman, A.S., Weddige, F.K., Lipinski, J.L., Jr. Effect of glucose on antipsychotic drug-induced changes in dopamine neuronal activity. Eur. J. Pharmacol., 431: 43-46, 2001.
Hamilton, M.E., Weddige, F.K. and Freeman, A.S. Effects of forebrain microinjection of cholecystokinin on dopamine cell firing rate. Peptides 22:1063-1069, 2001.
Hamilton, M.E., Redondo, J.-L. and Freeman, A.S. Overflow of dopamine and cholecystokinin in rat nucleus accumbens in response to acute drug administration. Synapse 38:238-242, 2000.
Hamilton, M.E. and Freeman, A.S. Effects of intra-midbrain injection of cholecystokinin on dopamine overflow in nucleus accumbens and amygdala: in vivo microdialysis in freely moving rats. Brain Res. 688:134-142, 1995
Parikh, H., Chiodo, L.A., Sibley, D.R., Rubin, J. and Freeman. A.S. Cholecystokinin mobilizes intracellular Ca2+ in hybrid N18TG2 X mesencephalon cells. Synapse 21:278-280, 1995.
Freeman, A.S. Interactions between dopamine and cholecystokinin in the brain. In: The Modulation of Dopaminergic Neurotransmission by Other Neurotransmitters, C.R. Ashby Jr., ed., CRC Press, Boca Raton, pp. 123-156, 1996.
Zhang, J. and Freeman, A.S. Influence of excitatory amino acid receptor subtypes on the electrophysiological activity of dopaminergic and nondopaminergic neurons in rat substantia nigra. J. Pharmacol. Exp. Ther. 269:313-321, 1994.
Zhang, J. and Freeman, A.S. Electrophysiological effects of cholecystokinin on neurons in rat substantia nigra pars reticulata. Brain Res. 652:154-156, 1994.
Freeman, A.S., Chiodo, L.A., Lentz, S., Wade, K. and Bannon, M.J. Release of CCK from midbrain slices and modulatory influence of D2 DA receptor stimulation. Brain Res. 555:281-287, 1991.
For further information contact Dr.Arthur S. Freeman