KRISTEN A. KEEFE
Kristen Keefe
email: K.Keefe@utah.edu		 Associate Professor of Pharmacology and Toxicology

Brain and Behavior
Neurobiology of Disease
Cellular Neuroscience

B.S. 1984, Case Western Reserve University; M.S. 1989, University of Pittsburgh; Ph.D. 1992, University of Pittsburgh; Post-doctoral fellow 1992-1995, NIMH.

RESEARCH:

My laboratory is interested in the functional neuroanatomy of the basal ganglia, a group of subcortical nuclei in the brain involved in the control of movement and cognition, including habit formation and procedural learning. The importance of the basal ganglia for normal behavior is highlighted by the profound deficits observed in patients with Parkinson's disease, Huntington's disease, schizophrenia, and drug addiction -- diseases that are associated with dysfunction in the basal ganglia. Our work determines the influence of both endogenous and exogenous chemicals on the function of neurons in the basal ganglia in an attempt to better understand 1) the role that glutamate (via NMDA receptors) and monoamines (dopamine and serotonin) play in regulating the activity of basal ganglia nuclei, 2) the mechanisms by which drugs of abuse procude long-term alterations in basal ganglia function, and 3) the mechanisms by which the function of the basal ganglia can be beneficially altered by drugs to better treat sequelae associated with dysfunction in these nuclei.

We use numerous techniques to examine basal ganglia function including: 1) in vivo microdialysis; 2) in situ hybridization histochemistry; 3) immunohistochemistry; 4) in vitro, whole-cell patch-clamp electrophysiology; 5) behavioral analyses.

Coupling these techniques, we can begin to understand how neurotransmitters and drugs acutely affect the function of basal ganglia neurons and the neuroadaptive changes that occur in response to neural injury in the basal ganglia and exposure to therapeutic and abused drugs.

Selected Publications

Horner, K. A., and Keefe, K. A. (2006) Regulation of psychostimulant-induced preprodynorphin, c-fos, and zif/268 messenger RNA expression in the rat dorsal striatum by mu opioid receptor blockade. European Journal of Pharmacology, 532:61-73.

Daberkow, D. P., Kesner, R. P., and Keefe, K. A. (2005) Relation of methamphetamine-induced monoamine loss to basal ganglia-dependent learning. Pharmacology, Biochemistry, and Behavior, 81:198-204.

Chapman, D. E., Keefe, K. A., and Wilcox, K. S. (2003) Evidence for functionally distinct synaptic NMDA receptors in ventromedial versus dorsolateral striatum. Journal of Neurophysiology, 89:69-80.

Adams, D. H., Hanson, G. R., and Keefe, K. A. (2003) Distinct effects of methamphetamine and cocaine on preprodynorphin messenger RNA in rat striatal patch and matrix. The Journal of Neurochemistry, 84:87-93.

Johnson-Davis, K. L., Hanson, G. R., and Keefe, K. A. (2003) Lack of effect of k-opioid receptor agonism on long-term methamphetamine-induced neurotoxicity in rats. Neurotoxicity Research, 5:273-282.

Johnson-Davis, K. L., Hanson, G. R., and Keefe, K. A. (2002) Long-term post-synaptic consequences of methamphetamine on preprotachykinin mRNA expression. The Journal of Neurochemistry, 82:1472-1479.

Ganguly, A., and Keefe, K. A. (2001) Unilateral dopamine depletion increases expression of the NR2A subunit of the NMDA receptor in enkephalin-positive and enkephalin-negative striatal neurons. Neuroscience, 103:405-412.

Chapman, D. E., Hanson, G. R., Kesner, R. P., and Keefe, K. A. (2001) Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine. The Journal of Pharmacology and Experimental Therapeutics 296:520-527.

Hanson, G. R., and Keefe, K. A. (1999) Dopamine D-1 regulation of caudate neurotensin mRNA in the presence or absence of the nigrostriatal dopamine pathway. Molecular Brain Research 66:111-121.

Keefe, K. A., and Ganguly, A. (1998) Effects of NMDA receptor antagonists on D1 dopamine receptor-mediated changes in striatal immediate early gene expression: Evidence for involvement of pharmacologically distinct NMDA receptors? Developmental Neuroscience 20:216-228.

Keefe, K. A., and Adams, A. C. (1998) Differential effects of NMDA receptor blockade on eticlopride-induced immediate early gene expression in the medial and lateral striatum. JPET 287:1076-1083.

Keefe, K. A., and Gerfen, C. R. (1998) Local infusion of the AMPA/kainate receptor antagonist CNQX does not block D1 dopamine receptor-mediated increases in immediate early gene expression. Neuroscience 89:491-504.

Keefe, K. A., and Gerfen, C. R. (1996) D1 dopamine receptor-mediated induction of zif268 and c-fos in the dopamine-depleted striatum: Differential regulation and independence from NMDA receptors. The Journal of Comparative Neurology 367:165-176.

Gerfen, C. R., Keefe, K. A., and Gauda, E. B. (1995) D1 and D2 dopamine receptor function in the striatum: Coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons. The Journal of Neuroscience 15(12): 8167-8176.

Keefe, K. A., Sved, A. F., Zigmond, M. J., and Abercrombie, E. D. (1993) Stress-induced dopamine release in the neostriatum: Evaluation of the role of action potentials in nigrostriatal dopamine neurons or local initiation by endogenous excitatory amino acids. Journal of Neurochemistry 61: 943-1952.

Neuroscience Home Page Contact us Search