title: Effects of nicotine administration on striatal dopamine signaling after traumatic brain injury in rats.
abstract: Previous studies on the therapeutic potential of agents affecting the dopamine system in traumatic brain injury (TBI) suggest that dopamine dysregulation may have a major role in behavioral deficit after TBI. We have previously identified that TBI reduces striatal dopamine synthesis and release at 7 days post-injury. In order to reverse deficits in the activity of tyrosine hydroxylase and dopamine release following TBI, we administered nicotine by intraperitoneal injection into rats for 7 days. Tyrosine hydroxylase activity assay demonstrated recovery of activity with nicotine treatment in injured animals. Microdialysis experiments using potassium stimulation to induce dopamine release showed recovery of dopamine release in injured animals receiving nicotine treatment. There was no effect of nicotine injection on extracellular dopamine metabolite levels, indicating the specificity of nicotine's effect on dopamine synthesis and release. Also, the activation of downstream postsynaptic molecule dopamine and cAMP regulated phosphoprotein 32 (DARPP-32) was assessed by Western blots for DARPP-32 phosphorylated at threonine 34 (pDARPP-32-T34). Injury reduced pDARPP-32-T34 levels, but nicotine treatment of injured animals did not alter pDARPP-32-T34 levels, indicating that postsynaptic dopamine signaling is complex, and the recovery of dopamine release may not be sufficient for the recovery of DARPP-32 activity.
authors.affiliation: Brain Trauma Research Center, Department of Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Shin
authors.forename: Eric R
authors.initials: ER
authors.lastname: Bray
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018722:Nicotinic Agonists; D009538:Nicotine; D004298:Dopamine