The role of neurokinin receptors in dopamine/acetylcholine signaling in the neostriatum during cocaine exposure.
Item
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Title
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The role of neurokinin receptors in dopamine/acetylcholine signaling in the neostriatum during cocaine exposure.
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Identifier
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AAI3047250
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identifier
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3047250
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Creator
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Noailles, Pierre-Antoine Harry.
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Contributor
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Adviser: Jesus Angulo
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Date
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2002
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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Neurokinin receptors (NKR) are ideally located in areas of the basal ganglia on subpopulations of interneurons to modulate cocaine evoked neurotransmitter release in the rat neostriatum. Basal ganglia nuclei modulate output behaviors such as feeding, maternal and sexual behavior. The striatum is the major input nuclei of the basal ganglia and the main neurotransmitter is dopamine (DA). Altered DA activity may be responsible for plastic changes in the basal ganglia.;Rats treated acutely (10mg/kg IP) and chronically (7 days) with cocaine exhibited a dose dependant decrease in DA release in the striatum resulting from intracranial co-administration of NK-1R antagonists (WIN 51,708, D-Arg 1, D-Pro2, D-Trp7,9, Leu11 and L733,060). Administration of NK-3R antagonists (SR142801 and D-Pro 2, D-Trp6,8, Nle10) to animals that had been treated acutely with cocaine had no significant effect on cocaine evoked dopamine release. In animals treated chronically with cocaine, NK-3R antagonists reduced cocaine evoked dopamine efflux. Direct administration of WIN 51,708 (10-4M) into the shell of the nucleus accumbens (NAcSHELL) significantly reduced cocaine evoked DA release.;Acetylcholine (ACh) is a major modulator of DA neurochemistry in the striatum and NAc of the rat and cholinergic interneurons have NK-1R on their soma and dendrites. Direct intrastriatal administration of WIN 51,708 (10 -4M) caused a complete repression of cocaine evoked ACh release in that region in acutely and chronically treated rats. I used immunocytochemisty (ICC) to visualize NK-1R on cholinergic interneurons using antibodies for choline acetyltransferase (ChAt), an enzyme for the synthesis of acetylcholine, and NK-1R antibodies as markers. I found that administration of substance P (SP) caused a marked alteration in the pattern of immunoreactivity (IR) consistent with receptor internalization. Systemic cocaine administration caused a pattern of IR identical to that of the SP perfused animals. Pre-perfusion with the NK-1R antagonist WIN 51,708 blocked the cocaine evoked receptor internalization. An understanding of the role of substance P will help to elucidate mechanisms of cocaine-induced neuroplasticity and perhaps other neurochemical substrates of plasticity via peptidergic activity in other areas of the CNS.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
