Effects of dizocilpine (MK 801) on noradrenaline, serotonin and dopamine release and uptake.
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 microM) 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.
Callado
L F
LF
Academic Department of Anaesthesia and Intensive Care, St Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, UK.
Hopwood
S E
SE
Hancock
P J
PJ
Stamford
J A
JA
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D004563:Electrochemistry; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D012701:Serotonin; D016291:Dizocilpine Maleate; D004298:Dopamine; D009638:Norepinephrine