Differential effects of morphine- and cocaine-induced nNOS immunoreactivity in the dentate gyrus of hippocampus of mice lacking mu-opioid receptors.
This study investigated the expression of nNOS after repeated morphine or cocaine administration in order to determine if nNOS (neuronal nitric oxide synthase) is involved in the morphine- or cocaine-induced behavioral sensitization in mu-opioid receptor knockout (MOR(-/-)) mice. Higher numbers of nNOS-positive cells were observed in the dentate gyrus of the hippocampus (DG) of the wild-type (MOR(+/+)) mice repeatedly treated with either morphine or cocaine than in the saline treated MOR(+/+) mice (morphine, +122%; cocaine, +82%). Moreover, the MOR(-/-) mice also showed significantly higher morphine- or cocaine-induced nNOS expression levels in the DG than in the saline treated MOR(+/+) mice (morphine, +234%; cocaine, +54%). The MOR(-/-) mice showed a significantly higher morphine-induced nNOS expression level (+103%) or a lower cocaine-induced nNOS expression level (+38%) in the DG than in the morphine- or cocaine-treated MOR(+/+) mice. These results suggest that morphine and cocaine sensitization is differentially regulated by the mu-opioid receptors in MOR(-/-) mice via the nNOS systems in the DG.
Yoo
Ji-Hoon
JH
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Cho
Jae-Han
JH
Lee
Seok-Yong
SY
Lee
Sanggeol
S
Loh
Horace H
HH
Ho
Ing K
IK
Jang
Choon-Gon
CG
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000172:deficiency*
D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D017450:Receptors, Opioid, mu; D009020:Morphine; D052248:Nitric Oxide Synthase Type I; D003042:Cocaine