Abstract

The primary objective is to elucidate the mode of action of antipsychotic and psychotomimetic drugs in the CNS and to study influences of neurotransmitter systems on dopamine (DA) neurons with the goal being to develop new type of antipsychotic drugs (APD's) with minimum neurological side effects. There are three specific aims for the coming year: 1. To continue studies of long-term effects of antipsychotic and psychotomimetic drugs on catecholamine system. 2. To continue studies of influences of neuroregulator systems on identified DA neurons. 3. To continue studies on the functional significance of the coexistence of DA and cholecystokinin (CCK). Combinations of single unit recording, microiontophoretic (or micropressure) administration of drugs, electrical stimulation, lesions by neurotoxins, radioligand receptor binding, push-pull cannula local perfusion, release of DA and CCK from brain slices, measurement of biogenic amines and CCK levels by HPLC-EC and radioimmunoassay, retrograde tracing and immunocytochemical staining techniques will be used to achieve the goals. In particular, the experiments with long-term effects of APD's will be extended to unanesthetized preparations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH000378-07
Application #
3069731
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Edwards, E; Ashby, C R; Wang, R Y (1993) Further characterization of 5-HT- and 5-HT3 receptor agonists'-stimulated phosphoinositol phosphates accumulation. Brain Res 617:113-9
Ashby Jr, C R; Edwards, E; Wang, R Y (1992) Action of serotonin in the medial prefrontal cortex: mediation by serotonin3-like receptors. Synapse 10:7-15
Batsche, K; Granoff, M I; Wang, R Y (1992) 5-HT3 receptor antagonists fail to block the suppressant effect of cocaine on the firing rate of A10 dopamine neurons in the rat. Brain Res 592:273-7
Minabe, Y; Ashby Jr, C R; Wang, R Y (1992) Effects produced by acute and chronic treatment with granisetron alone or in combination with haloperidol on midbrain dopamine neurons. Eur Neuropsychopharmacol 2:127-33
Minabe, Y; Ashby Jr, C R; Heyser, C et al. (1992) The effects of prenatal cocaine exposure on spontaneously active midbrain dopamine neurons in adult male offspring: an electrophysiological study. Brain Res 586:152-6
Edwards, E; Ashby Jr, C R; Wang, R Y (1992) (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane(DOI) and alpha-methyl-5-HT: 5-HT2 receptor agonistic action on phosphatidylinositol metabolism in the rat fronto-cingulate and entorhinal cortex. Neuropharmacology 31:615-21
Edwards, E; Ashby, C R; Wang, R Y (1992) Biochemical characterization of phosphoinositide hydrolysis stimulated by 5-HT3 receptor agonists. Neuroreport 3:1081-4
Edwards, E; Harkins, K; Ashby Jr, C R et al. (1991) Effect of 5-hydroxytryptamine3 receptor agonists on phosphoinositides hydrolysis in the rat fronto-cingulate and entorhinal cortices. J Pharmacol Exp Ther 256:1025-32
Ashby Jr, C R; Minabe, Y; Edwards, E et al. (1991) Comparison of the effects of various typical and atypical antipsychotic drugs on the suppressant action of 2-methylserotonin on medial prefrontal cortical cells in the rat. Synapse 8:155-61
Pan, H S; Wang, R Y (1991) MDMA: further evidence that its action in the medial prefrontal cortex is mediated by the serotonergic system. Brain Res 539:332-6

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