title: Involvement of the Striatal Medium Spiny Neurons of the Direct Pathway in the Motor Stimulant Effects of Phencyclidine.
abstract: The psychotomimetic phencyclidine (PCP) produces behavioral symptoms similar to those observed in schizophrenia, accompanied by increased motor activity. The dopamine and adenosine 3',5'-cyclic monophosphate-regulated phosphoprotein of 32kDa (DARPP-32) is enriched in the medium spiny neurons (MSNs) of the striatum and has been implicated in the actions of PCP. We examined the effects of deletion of DARPP-32 in distinct populations of striatal MSNs, on the ability of PCP to induce motor activation and memory deficit.
  
  
  
  The effects of PCP were examined in mice with conditional knockout of DARPP-32 in the MSNs of the direct, or indirect pathway. DARPP-32 phosphorylation was determined by Western blotting. The motor stimulant effects of PCP were determined by measuring locomotion following acute and chronic administration. Memory deficit was evaluated using the passive avoidance test.
  
  
  
  Loss of DARPP-32 in direct MSNs prevents PCP-induced phosphorylation and abolishes the motor stimulation effects of PCP. In contrast, lack of DARPP-32 in indirect MSNs does not affect the ability of PCP to promote DARPP-32 phosphorylation and to increase motor activity. The impairment in passive avoidance induced by PCP is independent of the expression of DARPP-32 in direct or indirect MSNs.
  
  
  
  The increase in DARPP-32 phosphorylation induced by PCP occurs selectively in the MSNs of the direct pathway, which are also specifically involved in the motor stimulant effects of this drug. The memory deficit induced by PCP is not linked to the expression of DARPP-32 in striatal MSNs.
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden (Drs Bonito-Olivia, Madjid, Ögren, and Fisone, and Ms DuPont).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonito-Oliva
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden (Drs Bonito-Olivia, Madjid, Ögren, and Fisone, and Ms DuPont).
authors.forename: Caitlin
authors.initials: C
authors.lastname: DuPont
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden (Drs Bonito-Olivia, Madjid, Ögren, and Fisone, and Ms DuPont).
authors.forename: Nather
authors.initials: N
authors.lastname: Madjid
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden (Drs Bonito-Olivia, Madjid, Ögren, and Fisone, and Ms DuPont).
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Ögren
authors.affiliation: Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden (Drs Bonito-Olivia, Madjid, Ögren, and Fisone, and Ms DuPont). gilberto.fisone@ki.se.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fisone
keywords: basal ganglia; dopamine and cAMP-regulated phosphoprotein of 32 kDa; motor activity; phencyclidine; schizophrenia