title: Differential distribution of parvalbumin immunoreactive neurons in the striatum of cocaine sensitized rats.
abstract: Intermittent administration of psychostimulants such as cocaine and amphetamine can result in behavioral sensitization, which is believed to model the onset of drug addiction, as well as possible neural adaptations that lead to addictive behaviors. The dorsal striatum and the nucleus accumbens (NAc) have been shown to play an integral role in this phenomenon. However, these structures comprise a complex neuroanatomical organization, and few studies have correlated anatomical differentiation within these brain regions with functional (i.e. behavioral) outcome, particularly after psychostimulant exposure. Parvalbumin (PV)-containing GABAergic interneurons are a key neuronal cell population that can significantly regulate input-output functions in these brain regions. The present study quantified parvalbumin-immunoreactive cells in subterritories of the striatum and NAc in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for 5 consecutive days). Two or 14 days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the striatum (including the NAc) were processed for parvalbumin immunoreactivity, and the number of immunoreactive neurons was quantified. Repeated cocaine administration resulted in robust sensitization that correlated with transient increases in the number of PV immunoreactive neurons in the ventrolateral, dorsolateral and dorsomedial striatum. After a 2-week withdrawal period, sensitized animals showed a significant decrease in the number of PV+ neurons in the ventrolateral shell of the NAc and dorsomedial striatum, and no significant difference in any other area examined. These data suggest a dichotomous role for PV interneurons in different subterritories of the striatum and NAc during the short-term (induction) vs. long-term (expression) phases of cocaine sensitization.
authors.affiliation: Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 001, 115 Mill Street, Belmont, MA 02478, USA. mtodtenkopf@mclean.harvard.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Todtenkopf
authors.forename: J R
authors.initials: JR
authors.lastname: Stellar
authors.forename: E A
authors.initials: EA
authors.lastname: Williams
authors.forename: D S
authors.initials: DS
authors.lastname: Zahm
mesh_terms: D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D003042:Cocaine