title: Long-term administration of cocaine or serotonin reuptake inhibitors results in anatomical and neurochemical changes in noradrenergic, dopaminergic, and serotonin pathways.
abstract: The catechol and indole pathways are important components underlying plasticity in the frontal cortex and basal ganglia. This study demonstrates that administering rats either cocaine or a selective serotonin (or 5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) for 16 weeks results in reduced density of dopaminergic and noradrenergic terminals in the striatum and olfactory bulb, respectively, reflecting pruning of the terminal arbor of ventral midbrain dopaminergic and locus coeruleus noradrenergic neurones. In the striatum of cocaine-treated animals, basal dopamine levels, as well as cocaine-induced dopamine release, is diminished compared with controls. In contrast, serotonergic fibers, projecting from the raphe, sprout and have increased terminal density in the lateral septal nucleus and frontal cortex, following long-term cocaine or SSRI treatment. This is associated with elevated basal 5-HT and enhanced cocaine-induced 5-HT release in the frontal cortex. The anatomical and neurochemical changes in serotonergic fibers following cocaine or SSRI treatment may be explained by attenuated 5-HT(1A) autoreceptor function in the raphe. This study demonstrates extensive plasticity in the morphology and neurochemistry of the catechol and indole pathways that contribute to drug-induced plasticity of the corticostriatal (and other) projections. Moreover, our data suggest that drug-induced plastic adaptation is anatomically widespread and consequently, likely to have multiple and complex consequences.
authors.affiliation: Brain Injury and Repair, Howard Florey Institute, and Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia. malcolm.horne@florey.edu.au
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Horne
authors.forename: Joohyung
authors.initials: J
authors.lastname: Lee
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Katherine
authors.initials: K
authors.lastname: Lanning
authors.forename: Doris
authors.initials: D
authors.lastname: Tomas
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013995:Time
chemical_list: D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors