title: Differential changes in synaptic terminal protein expression between nucleus accumbens core and shell in the amphetamine-sensitized rat.
abstract: Repeated, intermittent administration of psychostimulant drugs such as D-amphetamine (AMPH) produces a state of behavioral sensitization to the drug that can last up to weeks to months. The molecular basis of this enhanced sensitivity to AMPH is poorly understood; however, adaptive changes in the mesocorticolimbic dopamine system has been postulated to be of primary importance. In the present investigation we used Western blotting to examine the expression of candidate presynaptic proteins involved in regulating neurotransmitter release and synaptic plasticity. Specifically, syntaxin 1, synaptophysin and synapsin I protein levels were examined in the nucleus accumbens (Nacc) and ventral tegmental area (VTA) of Sprague-Dawley rats following AMPH-sensitization. Animals received five repeated administrations of AMPH (1.5 mg/kg, i.p. on alternate days) followed by 14 days of withdrawal. Levels of syntaxin 1 and synaptophysin were found to be significantly reduced in the Nacc core of sensitized animals compared to saline-treated and untreated controls. However, syntaxin 1 expression was significantly increased in the Nacc shell subregion of sensitized animals. No significant difference in the level of synapsin I was noted in any of the brain regions. Further, expression of none of the synaptic proteins was significantly altered in the VTA of sensitized animals. Given the importance of syntaxin and synaptophysin in learning and memory processes and in the regulation of neurotransmitter release, changes in these proteins suggest their involvement in the associative learning aspects of sensitization and differential neurotransmitter release in the Nacc subregions.
authors.affiliation: Departments of Psychiatry and Neurology and Neurosurgery, Douglas Hospital Research Centre, McGill University, 6875 LaSalle Boulevard, Verdun, Montreal, Quebec H4H 1R3, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Subramaniam
authors.forename: E R
authors.initials: ER
authors.lastname: Marcotte
authors.forename: L K
authors.initials: LK
authors.lastname: Srivastava
mesh_terms: D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D016708:Synaptophysin / Q000187:drug effects / Q000378:metabolism; D050827:Syntaxin 1; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; C494213:Stx1a protein, rat; D016704:Synapsins; D016708:Synaptophysin; D050827:Syntaxin 1; D003913:Dextroamphetamine; D004298:Dopamine