title: Transactivation of TrkB by Sigma-1 receptor mediates cocaine-induced changes in dendritic spine density and morphology in hippocampal and cortical neurons.
abstract: Cocaine is a highly addictive narcotic associated with dendritic spine plasticity in the striatum. However, it remains elusive whether cocaine modifies spines in a cell type-specific or region-specific manner or whether it alters different types of synapses in the brain. In addition, there is a paucity of data on the regulatory mechanism(s) involved in cocaine-induced modification of spine density. In the current study, we report that cocaine exposure differentially alters spine density, spine morphology, and the types of synapses in hippocampal and cortical neurons. Cocaine exposure in the hippocampus resulted in increased spine density, but had no significant effect on cortical neurons. Although cocaine exposure altered spine morphology in both cell types, the patterns of spine morphology were distinct for each cell type. Furthermore, we observed that cocaine selectively affects the density of excitatory synapses. Intriguingly, in hippocampal neurons cocaine-mediated effects on spine density and morphology involved sigma-1 receptor (Sig-1 R) and its downstream TrkB signaling, which were not the case in cortical neurons. Furthermore, pharmacological inhibition of Sig-1 R prevented cocaine-induced TrkB activation in hippocampal neurons. Our findings reveal a novel mechanism by which cocaine induces selective changes in spine morphology, spine density, and synapse formation, and could provide insights into the cellular basis for the cognitive impairment observed in cocaine addicts.
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Minhan
authors.initials: M
authors.lastname: Ka
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Kook
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Liao
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Woo-Yang
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D000097605:Sigma-1 Receptor
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003042:Cocaine; D020813:Receptor, trkB; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor