Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine.

ABSTRACT

The adducin family of proteins associates with the actin cytoskeleton in a calcium-dependent manner. Beta adducin (ßAdd) is involved in synaptic plasticity in the hippocampus; however, the role of ßAdd in synaptic plasticity in other brain areas is unknown. Using diolistic labeling with the lipophilic dye DiI, we found that the density of mature mushroom-shaped spines was significantly decreased in the nucleus accumbens (NAc) in brain slices from ßAdd-knockout (KO) mice as compared to their wildtype (WT) siblings. The effect of 10 days of daily cocaine (15 mg/kg) administration on NAc spine number and locomotor behavior was also measured in ßAdd WT and KO mice. As expected, there was a significant increase in overall spine density in NAc slices from cocaine-treated WT mice at this time-point; however, there was a greater increase in the density of mushroom spines in ßAdd-KO animals following chronic cocaine administration than in WT. In addition, ßAdd-KO mice showed elevated locomotor activity in response to cocaine treatment compared to WT siblings. These results indicate that ßAdd is required for stabilising mature spines under basal conditions in the NAc, but that lack of this protein does not prevent synaptic remodeling following repeated cocaine administration. In addition, these data are consistent with previous studies suggesting that ßAdd may normally be involved in stabilising spines once drug- or experience-dependent remodeling has occurred.