The neuronal nitric oxide synthase (nNOS) gene contributes to the regulation of tyrosine hydroxylase (TH) by cocaine.
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 (20mg/kg) for 5 days. After 24h, 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.
Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA. mbalda@med.miami.edu
Mara A
MA
Balda
Karen L
KL
Anderson
Yossef
Y
Itzhak
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine