title: Phasic-like stimulation of the medial forebrain bundle augments striatal gene expression despite methamphetamine-induced partial dopamine denervation.
abstract: Methamphetamine-induced partial dopamine depletions are associated with impaired basal ganglia function, including decreased preprotachykinin mRNA expression and impaired transcriptional activation of activity-regulated, cytoskeleton-associated (Arc) gene in striatum. Recent work implicates deficits in phasic dopamine signaling as a potential mechanism linking methamphetamine-induced dopamine loss to impaired basal ganglia function. This study thus sought to establish a causal link between phasic dopamine transmission and altered basal ganglia function by determining whether the deficits in striatal neuron gene expression could be restored by increasing phasic dopamine release. Three weeks after pretreatment with saline or a neurotoxic regimen of methamphetamine, rats underwent phasic- or tonic-like stimulation of ascending dopamine neurons. Striatal gene expression was examined using in situ hybridization histochemistry. Phasic-like, but not tonic-like, stimulation induced immediate-early genes Arc and zif268 in both groups, despite the partial striatal dopamine denervation in methamphetamine-pretreated rats, with the Arc expression occurring in presumed striatonigral efferent neurons. Phasic-like stimulation also restored preprotachykinin mRNA expression. These results suggest that disruption of phasic dopamine signaling likely underlies methamphetamine-induced impairments in basal ganglia function, and that restoring phasic dopamine signaling may be a viable approach to manage long-term consequences of methamphetamine-induced dopamine loss on basal ganglia functions.
authors.affiliation: School of Biological Sciences, Illinois State University, Normal, Illinois, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Howard
authors.forename: Elissa D
authors.initials: ED
authors.lastname: Pastuzyn
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Barker-Haliski
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garris
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Keefe
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics; D003714:Denervation / Q000379:methods; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000235:genetics; D004558:Electric Stimulation / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology*; D008694:Methamphetamine / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000235:genetics
chemical_list: D000697:Central Nervous System Stimulants; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C092069:activity regulated cytoskeletal-associated protein; C044206:preprotachykinin; D008694:Methamphetamine; D004298:Dopamine