Rat‐strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self‐administration

Abstract

We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction.

3d Synaptic Organization of the Rat Ca1 and Alterations Induced by Cocaine Self-Administration

“…Taking both results together (regarding synaptic shape and size), cocaine-SA seems to induce an increase in the synaptic surface of axospinous AS, increasing both the proportion of synapses with more complex shapes and the size of macular synapses. In a previous study, we observed an increase in the proportion of larger dendritic spines in the Lewis rat CA1 after cocaine-SA 14 . We can therefore speculate that cocaine-SA causes an increase in synaptic activity and that this may induce the growth of macular synapses and, in some cases, lead to deep indentations and perforations appearing as the postsynaptic density (PSD) becomes larger (Supplementary figure 2).…”

“…Numerous studies have found that a variety of drugs of abuse produce several morphological modifications of the pyramidal neurons, including the dendritic spines, which represent the main postsynaptic target of excitatory glutamatergic synapses of the cerebral cortex 6 . These changes are found in different brain regions including the frontal cortex, hippocampus and the nucleus accumbens (e.g., 7,8,9,10,11,12,13,14 ). Previous studies in our laboratory have shown that cocaine-induced changes in the hippocampus depend on the rat strain; specifically, an increase in the dendritic spine density and the proportion of larger spines after cocaine self-administration (SA) in Lewis rats 13,14 .…”

“…These changes are found in different brain regions including the frontal cortex, hippocampus and the nucleus accumbens (e.g., 7,8,9,10,11,12,13,14 ). Previous studies in our laboratory have shown that cocaine-induced changes in the hippocampus depend on the rat strain; specifically, an increase in the dendritic spine density and the proportion of larger spines after cocaine self-administration (SA) in Lewis rats 13,14 . Several global and local processes, involving dendritic spine and synaptic reorganization (structural plasticity) occurring in a defined temporal manner, have been proposed to provide a mechanism for long-term storage of memory traces upon learning that influences behavior 15,16 .…”

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

“…After cocaine SA, proximal dendritic volume, dendritic surface area, and spine density were increased in LEW strain, where also an increased percentage of larger spines was observed. In contrast, F344 rats showed decreased spine head volume after cocaine SA (Selvas et al, 2015 ).…”

Automatic Dendritic Spine Quantification from Confocal Data with Neurolucida 360

“…Dendritic spine morphology has become a central focus in research in the fields of learning and memory, aging, and neurodegenerative diseases (for review see Dickstein et al, 2007;Hara et al, 2012;Dickstein et al, 2013) as well as other neuropsychiatric disorders such as autism (Hung et al, 2008;Hutsler and Zhang, 2010;Durand et al, 2012;Phillips and Pozzo-Miller, 2015), schizophrenia (Hayashi-Takagi et al, 2011;Ramos-Miguel et al, 2015), and addiction (Maze et al, 2010;Selvas et al, 2015) as they are an integral component of excitatory synapses. Excitatory synapses comprise the majority of connections in the central nervous system and play a vital role in learning, memory, and cognition.…”