Cytoskeletal proteins are important in protein trafficking, membrane protei
n clustering, dendrite growth and the morphological maintenance of neurons.
Sigma, receptors are unique endoplasmic reticular (ER) proteins that bind
(+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Coc
aine, via sigma, receptors, can cause the dissociation of a cytoskeletal ad
aptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P-3] r
eceptors on the ER as a sigma(1)-receptor-ankyrin complex, which then trans
locates to the plasma membrane and nucleus. The dissociation of sigma(1)-re
ceptor-ankyrin from Ins(1,4,5)P-3 receptors also increases the intracellula
r Ca2+ concentration ([Ca2+], which affects the activity of cytoskeletal pr
oteins. Furthermore, cocaine might increase [Ca2+](i) via phospholipase C (
PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause
life-long changes in neurons via cytoskeletal proteins by interacting with
both D1 receptors and sigma, receptors.