The effects of phencyclidine (PCP) on catecholaminergic neuronal pathways in the mammalian central nervous system function will be studied using extracellular electrophysiological recordings from single neurons and using in vivo electrochemistry to measure catecholamine transmitter release in vivo. We will apply drugs locally in situ and to isolated neuronal circuits transplanted in oculo by microiontrophoresis and by pressure ejection form multibarrel micropipettes. Drugs will also be applied by superfusion and by eyedrops to the intraocular brain grafts, and i.p. to the whole animal. We have characterized catecholomimetic PCP effects in the cerebellar cortex, hippocampus and prefrontal cortex electrophysiologically, and we have studied PCP effects on dopamine release in the caudate nucleus. We will electrophysiologically characterize PCP interactions with norepinephrine synapses in the prefrontal cortex and with dopamine in the accumbens. We will also investigate PCP interactions with kappa and sigma agonists, we will study changes in PCP effects with chronic exposure, and we will investigate if PCP interactions with dopamine synapses are altered in animals that self-administer PCP. Finally we will determine if the PCP effects observed in rat models are similarly produced in human brain xenographs in oculo in rats. A greater understanding of how ethanol alters CNS function should furnish new insights into the problems of PCP abuse and could lead to pharmacological approaches to eliminate the unwanted effects of this psychotomimetic drug without changing its beneficial qualities.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002429-11
Application #
3207329
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1979-08-01
Project End
1991-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Kim, M; Bickford, P C (1992) Electrophysiological effects of phencyclidine and the sigma agonist ditolylguanidine in the cerebellum of the rat. Neuropharmacology 31:77-83
Miller, C L; Bickford, P C; Luntz-Leybman, V et al. (1992) Phencyclidine and auditory sensory gating in the hippocampus of the rat. Neuropharmacology 31:1041-8
Kao, M C; Lee, H K; Chai, C Y et al. (1991) NMDA antagonists attenuate hypertension induced by carotid clamping in the rostral ventrolateral medulla of rats. Brain Res 549:83-9
Wang, Y; Lee, H K (1991) Electrophysiological interactions between NMDA and phencyclidine/sigma receptor agonists and antagonists in Purkinje neurons in the cerebellum of the rat. Neuropharmacology 30:985-94
Gratton, A; Hoffer, B J; Gerhardt, G A (1989) In vivo electrochemical studies of monoamine release in the medial prefrontal cortex of the rat. Neuroscience 29:57-64
Gerhardt, G A; Drebing, C J; Stephen, C et al. (1989) Direct determination of unconjugated HVA in human plasma filtrates by HPLC coupled with dual-electrode coulometric electrochemical detection. Biomed Chromatogr 3:105-9
de la Garza, R; Freedman, R; Hoffer, B J (1989) Kappa-bungarotoxin blockade of nicotine electrophysiological actions in cerebellar Purkinje neurons. Neurosci Lett 99:95-100
de la Garza, R; Freedman, R; Hoffer, J (1989) Nicotine-induced inhibition of cerebellar Purkinje neurons: specific actions of nicotine and selective blockade by mecamylamine. Neuropharmacology 28:495-501
Gratton, A; Hoffer, B J; Gerhardt, G A et al. (1988) Potentiation of morphine-elicited circling by dopaminergic uptake blockade. Pharmacol Biochem Behav 30:1077-9
Gratton, A; Hoffer, B J; Gerhardt, G A (1988) Effects of electrical stimulation of brain reward sites on release of dopamine in rat: an in vivo electrochemical study. Brain Res Bull 21:319-24

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