The synaptic adhesion molecule SynCAM 1 contributes to cocaine effects on synapse structure and psychostimulant behavior

Joanna I. Giza, Yonwoo Jung, Rachel A. Jeffrey, Nichole M. Neugebauer, Marina R. Picciotto, Thomas Biederer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Drugs of abuse have acute and persistent effects on synapse structure and addiction-related behaviors. Trans-synaptic interactions can control synapse development, and synaptic cell adhesion molecule (SynCAM) proteins (also named nectin-like molecules) are immunoglobulin adhesion proteins that span the synaptic cleft and induce excitatory synapses. Our studies now reveal that the loss of SynCAM 1 in knockout (KO) mice reduces excitatory synapse number in nucleus accumbens (NAc). SynCAM 1 additionally contributes to the structural remodeling of NAc synapses in response to the psychostimulant cocaine. Specifically, we find that cocaine administration increases the density of stubby spines on medium spiny neurons in NAc, and that maintaining this increase requires SynCAM 1. Furthermore, mushroom-type spines on these neurons are structurally more plastic when SynCAM 1 is absent, and challenging drug-withdrawn mice with cocaine shortens these spines in SynCAM 1 KO mice. These effects are correlated with changes on the behavioral level, where SynCAM 1 contributes to the psychostimulant effects of cocaine as measured after acute and repeated administration, and in drug-withdrawn mice. Together, our results provide evidence that the loss of a synapse-organizing adhesion molecule can modulate cocaine effects on spine structures in NAc and increases vulnerability to the behavioral actions of cocaine. SynCAM-dependent pathways may therefore represent novel points of therapeutic intervention after exposure to drugs of abuse.

Original languageEnglish (US)
Pages (from-to)628-638
Number of pages11
JournalNeuropsychopharmacology
Volume38
Issue number4
DOIs
StatePublished - Mar 2013

Keywords

  • CADM
  • MSN
  • SynCAM
  • cocaine
  • nectin-like molecule
  • synapse

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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