TY - JOUR
T1 - The neuronal nitric oxide synthase (nNOS) gene contributes to the regulation of tyrosine hydroxylase (TH) by cocaine
AU - Balda, Mara A.
AU - Anderson, Karen L.
AU - Itzhak, Yossef
N1 - Funding Information:
This work was supported by awards RO1 DA019107 (YI) and F30 DA022847-01 (MB) from the National Institute on Drug Abuse.
PY - 2009/7/3
Y1 - 2009/7/3
N2 - Recently, we demonstrated that intact nitric oxide (NO) signaling is essential for the development of cocaine behavioral sensitization in adulthood [M.A. Balda, K.L. Anderson, Y. Itzhak, Differential role of the nNOS gene in the development of behavioral sensitization to cocaine in adolescent and adult B6;129S mice, Psychopharmacology (Berl) 200 (2008) 509-519]. Given the requirement of dopamine (DA) transmission in cocaine-induced behavioral sensitization and the interactions between NO and DA systems, the present study investigated the role of the neuronal nitric oxide synthase (nNOS) gene and the effect of cocaine on the expression of tyrosine hydroxylase (TH)-immunoreactive (-ir) neurons. Adult (postnatal day 80) wild type (WT) and nNOS knockout (KO) mice received saline or a sensitizing regimen of cocaine (20 mg/kg) for 5 days. After 24 h, TH immunoreactivity was assessed in the ventral tegmental area (VTA) and the dorsal striatum (dST) using stereology and Western blotting, respectively. We report that (a) nNOS KO mice express lower levels of TH-ir neurons in the VTA compared to WT counterparts, (b) cocaine administration to WT mice significantly increased striatal TH expression, and (c) the same cocaine administration to nNOS KO mice significantly decreased striatal TH expression. Thus, the nitrergic system may contribute to cocaine-induced behavioral sensitization by regulating dopaminergic neurotransmission.
AB - Recently, we demonstrated that intact nitric oxide (NO) signaling is essential for the development of cocaine behavioral sensitization in adulthood [M.A. Balda, K.L. Anderson, Y. Itzhak, Differential role of the nNOS gene in the development of behavioral sensitization to cocaine in adolescent and adult B6;129S mice, Psychopharmacology (Berl) 200 (2008) 509-519]. Given the requirement of dopamine (DA) transmission in cocaine-induced behavioral sensitization and the interactions between NO and DA systems, the present study investigated the role of the neuronal nitric oxide synthase (nNOS) gene and the effect of cocaine on the expression of tyrosine hydroxylase (TH)-immunoreactive (-ir) neurons. Adult (postnatal day 80) wild type (WT) and nNOS knockout (KO) mice received saline or a sensitizing regimen of cocaine (20 mg/kg) for 5 days. After 24 h, TH immunoreactivity was assessed in the ventral tegmental area (VTA) and the dorsal striatum (dST) using stereology and Western blotting, respectively. We report that (a) nNOS KO mice express lower levels of TH-ir neurons in the VTA compared to WT counterparts, (b) cocaine administration to WT mice significantly increased striatal TH expression, and (c) the same cocaine administration to nNOS KO mice significantly decreased striatal TH expression. Thus, the nitrergic system may contribute to cocaine-induced behavioral sensitization by regulating dopaminergic neurotransmission.
KW - Behavioral sensitization
KW - Cocaine
KW - Dorsal striatum (dST)
KW - Neuronal nitric oxide synthase (nNOS)
KW - Stereology
KW - Tyrosine hydroxylase (TH)
KW - Ventral tegmental area(VTA)
KW - Western blotting
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U2 - 10.1016/j.neulet.2009.04.011
DO - 10.1016/j.neulet.2009.04.011
M3 - Article
C2 - 19429176
AN - SCOPUS:67349178229
VL - 457
SP - 120
EP - 124
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -