Altered dendritic spine plasticity in cocaine-withdrawn rats.
Chronic cocaine treatment is associated with changes in dendritic spines in the nucleus accumbens, but it is unknown whether this neuroplasticity alters the effect of a subsequent cocaine injection on spine morphology and protein content. Three weeks after daily cocaine or saline administration, neurons in the accumbens were filled with the lipophilic dye, DiI. Although daily cocaine pretreatment did not alter spine density compared with daily saline, there was a shift from smaller to larger diameter spines. During the first 2 h after an acute cocaine challenge, a bidirectional change in spine head diameter and increase in spine density was measured in daily cocaine-pretreated animals. In contrast, no change in spine diameter or density was elicited by a cocaine challenge in daily saline animals during the first 2 h after injection. However, spine density was elevated at 6 h after a cocaine challenge in daily saline-pretreated animals. The time-dependent profile of proteins in the postsynaptic density subfraction elicited by a cocaine challenge in daily cocaine-pretreated subjects indicated that the changes in spine diameter and density were associated with a deteriorating actin cytoskeleton and a reduction in glutamate signaling-related proteins. Correspondingly, the amplitude of field potentials in accumbens evoked by stimulating prefrontal cortex was reduced for up to 6 h after acute cocaine in daily cocaine-withdrawn animals. These data indicate that daily cocaine pretreatment dysregulates dendritic spine plasticity elicited by a subsequent cocaine injection.
Shen
Hao-wei
HW
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Toda
Shigenobu
S
Moussawi
Khaled
K
Bouknight
Ashley
A
Zahm
Daniel S
DS
Kalivas
Peter W
PW
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D003042:Cocaine / Q000009:adverse effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008297:Male; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions; D013375:Substance Withdrawal Syndrome / Q000473:pathology* / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology
D000199:Actins; D003042:Cocaine