Nicotine normalizes increased prefrontal cortical dopamine D1 receptor binding and decreased working memory performance produced by repeated pretreatment with MK-801: a PET study in conscious monkeys.
The effects of acute nicotine were determined on dopamine (DA) D(1) (D(1)R) and D(2) (D(2)R) receptor binding in the neocortex of conscious monkeys under control conditions as well as after chronic pretreatment with MK-801 (dizocilpine), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Extrastriatal neocortical D(1)R and D(2)R binding was evaluated with [(11)C]NNC112 and [(11)C]FLB457 with high-specific radioactivity using positron emission tomography (PET). Acute administration of nicotine bitartrate, given as an intravenous (i.v.) bolus plus infusion for 30 min at doses of 32 microg/kg+0.8 microg/kg/min or 100 microg/kg+2.53 microg/kg/min as base, induced slight but significant dose-dependent increases of DA in the extracellular fluid of prefrontal cortex (PFC) as determined by microdialysis. However, acute nicotine did not affect either [(11)C]NNC112 or [(11)C]FLB457 binding to D(1)R or D(2)R, respectively, in any cortical region. Chronic MK-801 (0.03 mg/kg, intramuscularly (i.m.), twice daily for 13 days) increased [(11)C]NNC112 binding to D(1)R in PFC. No significant changes were detected in [(11)C]FLB457 binding to PFC D(2)R. Although chronic MK-801 lowered baseline DA and glutamate levels in PFC, acute nicotine normalized reduced DA to control levels. Acute nicotine dose-dependently normalized the increased binding of [(11)C]NNC112 to D(1)R produced by chronic MK-801 but [(11)C]FLB457 binding to PFC D(2)R did not change. Working memory performance, impaired after chronic MK-801, was partially improved by acute nicotine. These results demonstrate that acute nicotine normalizes MK-801-induced PFC abnormality of D(1)R in PFC.
Tsukada
Hideo
H
Central Research Laboratory, Hamamatsu Photonics KK, Hamakita, Shizuoka, Japan.
Miyasato
Katsumasa
K
Nishiyama
Shingo
S
Fukumoto
Dai
D
Kakiuchi
Takeharu
T
Domino
Edward F
EF
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001572:Benzofurans / Q000378:metabolism; D016291:Dizocilpine Maleate; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D008570:Memory, Short-Term / Q000187:drug effects*; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism*; D012457:Salicylamides
D001552:Benzazepines; D001572:Benzofurans; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D012457:Salicylamides; C065065:FLB 457; C077123:NNC 112; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009538:Nicotine; D004298:Dopamine