title: GABAergic control of neostriatal dopamine D2receptor binding and behaviors in the rat.
abstract: The present study assessed the influence of the GABAAreceptor agonist muscimol and the GABAAreceptor antagonist bicuculline on neostriatal dopamine D2receptor binding in relation to motor and exploratory behaviors in the rat.
  
  
  
  D2receptor binding was measured in baseline and after challenge with either 1mg/kg muscimol or 1mg/kg bicuculline. In additional rats, D2receptor binding was measured after injection of saline. After treatment with muscimol, bicuculline and saline, motor and exploratory behaviors were assessed for 30min in an open field prior to administration of [123I]S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide ([123I]IBZM). For baseline and challenges, striatal equilibrium ratios (V3″) were computed as estimation of the binding potential.
  
  
  
  Muscimol but not bicuculline reduced D2receptor binding relative to baseline and to saline. Travelled distance, duration of rearing and frequency of rearing and of head-shoulder motility were lower after muscimol compared to saline. In contrast, duration of rearing and grooming and frequency of rearing, head-shoulder motility and grooming were elevated after bicuculline relative to saline. Moreover, bicuculline decreased duration of sitting and head-shoulder motility.
  
  
  
  The muscimol-induced decrease of motor/exploratory behaviors can be related to an elevation of striatal dopamine levels. In contrast, bicuculline is likely to elicit a decline of synaptic dopamine, which, however, is compensated by the time of D2receptor imaging studies. The results indicate direct GABAergic control over D2receptor binding in the neostriatum in relation to behavioral action, and, thus, complement earlier pharmacological studies.
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. Electronic address: susanne.nikolaus@uni-duesseldorf.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nikolaus
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Beu
authors.affiliation: Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
authors.forename: Maria Angelica
authors.initials: MA
authors.lastname: de Souza Silva
authors.affiliation: Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Antke
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Müller
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hautzel
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D017072:Neostriatum / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D001549:Benzamides; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D001640:Bicuculline
keywords: Bicuculline; D(2) receptor; GABA(A) receptor; Muscimol; Small animal SPECT; Time-behavior curves; [(123)I]IBZM