Mu-opioid receptors modulate the stability of dendritic spines.
Opioids classically regulate the excitability of neurons by suppressing synaptic GABA release from inhibitory neurons. Here, we report a role for opioids in modulating excitatory synaptic transmission. By activating ubiquitously clustered mu-opioid receptor (MOR) in excitatory synapses, morphine caused collapse of preexisting dendritic spines and decreased synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Meanwhile, the opioid antagonist naloxone increased the density of spines. Chronic treatment with morphine decreased the density of dendritic spines even in the presence of Tetrodotoxin, a sodium channel blocker, indicating that the morphine's effect was not caused by altered activity in neural network through suppression of GABA release. The effect of morphine on dendritic spines was absent in transgenic mice lacking MORs and was blocked by CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2), a mu-receptor antagonist. These data together with others suggest that endogenous opioids and/or constitutive activity of MORs participate in maintaining normal morphology and function of spines, challenging the classical model of opioids. Abnormal alteration of spines may occur in drug addiction when opioid receptors are overactivated by exogenous opiates.
Liao
Dezhi
D
Department of Neuroscience and Basic Research Center on Molecular and Cell Biology of Drug Addiction, University of Minnesota, 321 Church Street SE, Minneapolis, MN 55455, USA. Liaox020@tc.umm.edu
Lin
Hang
H
Law
Ping Yee
PY
Loh
Horace H
HH
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D049229:Dendritic Spines / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D051381:Rats; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000502:physiology*
D010446:Peptide Fragments; D017450:Receptors, Opioid, mu