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Effects of dizocilpine (MK 801) on noradrenaline, serotonin and dopamine release and uptake

Callado, Luis F.1; Hopwood, Sarah E.1; Hancock, Pamela J.1; Stamford, Jonathan A.1,2

Neuropharmacology and Neurotoxicology

In the present study, we examined the actions of the NMDA antagonist dizocilpine (MK801) on electrically evoked release and uptake of noradrenaline (NA) in the locus coeruleus (LC), serotonin (5-HT) in the dorsal raphe nucleus (DRN) and dopamine (DA) in the nucleus accumbens (NAc), measured by fast cyclic voltammetry (FCV) in rat brain slices. Dizocilpine (10 μM) significantly increased NA (to 248 ± 15%) and 5-HT release (to 184 ± 29%) and slowed monoamine uptake in the LC (t1/2 = 853 ± 129%) and the DRN (t1/2 = 387 ± 70%), respectively. However, dizocilpine had no effect on DA release or uptake in NAc. Actions on monoamines are thus likely and should be considered in the interpretation of data regarding dizocilpine.

1Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, St Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel London EI IBB, UK

2Corresponding Author: Jonathan A. Stamford

Acknowledgements: L.F.C. holds a postdoctoral fellowship from the Basque Government. S.E.H. is supported by a grant from the RLH Special Trustees to J.A.S.

Received 21 September 1999; accepted 3 November 1999

© 2000 Lippincott Williams & Wilkins, Inc.