Cocaine- and morphine-induced synaptic plasticity in the nucleus accumbens.
The critical brain areas and molecular mechanisms involved in drug abuse and dependence have been extensively studied. Drug-induced persistent behaviors such as sensitization, tolerance, or relapse, however, far outlast any previously reported mechanisms. A challenge in the field of addiction, therefore, has been to identify drug-induced changes in brain circuitry that may subserve long-lasting changes in behavior. This study examined behavioral changes and electron microscopic evidence of altered synaptic connectivity within the nucleus accumbens (NAc) following repeated administration of cocaine or morphine. The unbiased quantitative stereological physical disector method was used to estimate the number of synapses per neuron. Increases in the synapse-to-neuron ratio were found in the NAc shell of cocaine-treated (49.1%) and morphine-treated (55.1%) rats and in the NAc core of cocaine-treated animals (49.1%). This study provides direct ultrastructural evidence of drug-induced synaptic plasticity and identifies synaptic remodeling as a potential neural substrate underlying drug-induced behavioral sensitization.
Alcantara
Adriana A
AA
Institute for Neuroscience, The University of Texas at Austin, Austin, Texas 78712, USA. aaalcantara@uh.edu
Lim
Helen Y
HY
Floyd
Christopher E
CE
Garces
Juanita
J
Mendenhall
John M
JM
Lyons
Chelsea L
CL
Berlanga
Monica L
ML
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D009020:Morphine; D003042:Cocaine