title: Dopamine and glutamate interaction mediates reinstatement of drug-seeking behavior by stimulation of the ventral subiculum.
abstract: BACKGROUND
  Drug addiction is a chronic brain disease characterized by recurrent episodes of relapse to drug-seeking/-taking behaviors. The ventral subiculum, the primary output of the hippocampus, plays a critical role in mediating drug-seeking behavior.
  
  
  METHODS
  A d-amphetamine intravenous self-administration rat model was employed along with focal electrical stimulation of the ventral subiculum (20 Hz/200 pulses) to examine its role in reinstatement of drug-seeking behavior. Dopamine efflux in the nucleus accumbens was measured by in vivo microdialysis and subsequent HPLC-ED analyses. Pharmacological antagonism of dopamine and ionotropic glutamate receptors locally within the nucleus accumbens was employed to assess the role of glutamate and dopamine in reinstatement of drug-seeking behavior induced by stimulation of the ventral subiculum.
  
  
  RESULTS
  Here, we demonstrate that reinstatement of drug-seeking behavior following extinction of d-amphetamine self-administration by rats was induced by electrical stimulation in the ventral subiculum but not the cortex. This reinstatement was accompanied by a significant increase in dopamine efflux in the nucleus accumbens and was disrupted by microinfusion of a dopamine D1 or D2 antagonist into the nucleus accumbens. Inhibition of N-methyl-D-aspartate or non- N-methyl-D-aspartate receptors had no effect on the reinstatement induced by ventral subiculum stimulation, whereas co-infusion of D1 and N-methyl-D-aspartate antagonists at formerly ineffective doses prevented drug-seeking behavior.
  
  
  CONCLUSIONS
  These data support the hypothesis that dopamine/glutamate interactions within the ventral striatum related to memory processes are involved in relapse to addictive behavior.
authors.affiliation: Department of Physiology, Naresuan University, Phitsanulok, Thailand (Dr Taepavarapruk); Department of Psychiatry, University of British Columbia, Vancouver, Canada (Drs Butts and Phillips).
authors.forename: Pornnarin
authors.initials: P
authors.lastname: Taepavarapruk
authors.affiliation: Department of Physiology, Naresuan University, Phitsanulok, Thailand (Dr Taepavarapruk); Department of Psychiatry, University of British Columbia, Vancouver, Canada (Drs Butts and Phillips).
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Butts
authors.affiliation: Department of Physiology, Naresuan University, Phitsanulok, Thailand (Dr Taepavarapruk); Department of Psychiatry, University of British Columbia, Vancouver, Canada (Drs Butts and Phillips). aphillips@psych.ubc.ca.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003913:Dextroamphetamine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000502:physiology*; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D020318:Rats, Long-Evans; D011954:Receptors, Dopamine / Q000378:metabolism; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012646:Self Administration; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D058468:Receptors, Ionotropic Glutamate; D015102:3,4-Dihydroxyphenylacetic Acid; D018698:Glutamic Acid; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid
keywords: deep brain-stimulation; dopamine amphetamine-reinstatement; nucleus accumbens; ventral subiculum