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Alterations in striatal acetylcholine overflow by cocaine, morphine, and MK-801: relationship to locomotor output

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Abstract

The activity of cholinergic interneurons in the striatum appears to be modulated by a variety of different systems including dopamine, opiate, and glutamate. The purpose of this study was to characterize the effects of drugs known to act on these three systems (i.e., cocaine, morphine, and MK-801) on striatal ACh overflow with microdialysis procedures, and to determine if alterations in ACh function induced by these agents are related to changes in locomotor activity. Cocaine was found to increase striatal ACh following intraperitoneal injections of 20 and 40 mg/kg, but not 10 mg/kg. The increases in locomotor activity induced by cocaine appeared to be dose dependent, while the effects on striatal ACh were not. Injections of 0.1 mg/kg MK-801 (a non-competitive NMDA receptor antagonist) produced dramatic increases in locomotor activity while decreasing striatal ACh overflow. A lower dose (0.03 mg/kg) of MK-801 failed to alter locomotor activity or striatal ACh. Morphine produced an apparent dose-dependent elevation in striatal ACh while only the lowest dose (5 mg/kg) increased locomotor activity. These appears to be no relationship between alterations in striatal ACh and locomotor output following systemic administration of these psychoactive agents.

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  1. Biological Psychiatry Branch, National Institute of Mental Health, Building 10, Room 3N212, 9000 Rockville Pike, 20892, Bethesda, Maryland, USA

    Alessandro Zocchi & Agu Pert

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  1. Alessandro Zocchi
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  2. Agu Pert
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Zocchi, A., Pert, A. Alterations in striatal acetylcholine overflow by cocaine, morphine, and MK-801: relationship to locomotor output. Psychopharmacology 115, 297–304 (1994). https://doi.org/10.1007/BF02245069

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