MK-801 elevates the extracellular concentration of dopamine in the rat prefrontal cortex and increases the density of striatal dopamine D1 receptors.
In the present study we found that MK-801 (dizocilpine), given peripherally in doses (0.2 and 0.4 mg/kg) which evoked locomotor activation in rats, enhanced in a dose-dependent manner the extracellular concentration of dopamine (DA) in the rat prefrontal cortex (PFC). MK-801 used in similar range of doses (0.2, 0.4 mg/kg) failed to alter the DA content in superfusates of the rat striatum (STR). It was also found that single doses of MK-801 enhanced the density of D1 receptors, assessed by the [3H]SCH 23390 binding in the rat STR, but not in the limbic forebrain. An increase in the density of D1 receptors was observed at 24, but not 2, h after MK-801 administration. MK-801 failed to alter the density of D2 receptors in the STR and limbic forebrain. The available data indicate that MK-801 may enhance the dopaminergic neurotransmission by at least two separate mechanisms: a fast one, associated with the release of DA in PFC, and a slow one, resulting from the increase in the D1 receptor density.
Wedzony
K
K
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Klimek
V
V
Gołembiowska
K
K
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism
D017447:Receptors, Dopamine D1; D016291:Dizocilpine Maleate; D004298:Dopamine