We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant Behavior.
- Authors
Giza, Joanna I; Jung, Yonwoo; Jeffrey, Rachel A; Neugebauer, Nichole M; Picciotto, Marina R; Biederer, Thomas
- 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mushroom-type spines on these neurons are structurally more plastic when SynCAM 1 is absent, and challenging drug-withdrawn mice with cocaine shortens these spines in SynCAM 1 KO mice.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contributes to the psychostimulant effects of cocaine as measured after acute and repeated administration, and in drug-withdrawn mice.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.
- Subjects
SYNAPSES; COCAINE; NECTINS; KNOCKOUT mice; NUCLEUS accumbens; NEURONS
- Publication
Neuropsychopharmacology, 2013, Vol 38, Issue 4, p628
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/npp.2012.226