The Effects of Cocaine Self-Administration on Dendritic Spine Density in the Rat Hippocampus Are Dependent on Genetic Background

Abstract

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.

Strain and cocaine-induced differential opioid gene expression may predispose Lewis but not Fischer rats to escalate cocaine self-administration

“…Fischer and Lewis rats differ also in their stress response (Dhabhar et al, 1993; Ergang et al, 2015) and impulsivity score (Hamilton et al, 2014; Madden et al, 2008), two features related to vulnerability to addiction. Overall, comparisons between Fischer and Lewis rats in cocaine self-administration have been carried out primarily in relatively short access self-administration paradigm (≤ 6h), rather than extended access (Freeman et al, 2009; Miguens et al, 2015; Rivera et al, 2013). Our laboratory has recently reported that Lewis rats escalate both cocaine and heroin intake to a greater extent than Fischer rats, in a new model of extended access (18h/day for 14 sessions) intravenous self-administration, in which rats are allowed to select the unit dose of drug to self-administer (Picetti et al, 2012; Picetti et al, 2010).…”

Male HIV‐1 transgenic rats show reduced cocaine‐maintained lever‐pressing compared to F344 wildtype rats despite similar baseline locomotion

“…The reduced cocaine sensitivity in Tg compared to WT rats emerged even with the relatively low cocaine self‐administration doses used in the current study and in some of the related literature (Bertrand et al, ; McIntosh et al, ; Wayman et al, ; Zhu et al, ). Indeed, research investigating this transgenic model should use the higher doses more common in cocaine self‐administration studies (Miguéns et al, ; Morgan, Liu, & Roberts, ) and provide a comparative background across strains. Further, the time taken for dopamine reuptake in striatal slices in HIV‐1 Tg rats is extended compared to WT controls (Javadi‐Paydar et al, ).…”

“…VR = variable ratio, FR = fixed ratio, Tg = transgenic. this transgenic model should use the higher doses more common in cocaine selfadministration studies (Miguéns et al, 2015;Morgan, Liu, & Roberts, 2006) and provide a comparative background across strains. Further, the time taken for dopamine reuptake in striatal slices in HIV-1 Tg rats is extended compared to WT controls (Javadi-Paydar et al, 2017).…”

Prenatal cocaine exposure and its impact on cognitive functions of offspring: a pathophysiological insight

“…Chronic COC exposure is related to structural changes of the CNS, specifically in areas involved in addiction (MacAskill et al, 2014;Miguens et al, 2015). Repeated treatment with COC has been reported to induce modifications in the architecture of dendrites and the density of dendritic spines on medium spiny neurons in the nucleus accumbens (NAc) and pyramidal cells in the prefrontal cortex (Robinson et al, 2001;Robinson and Kolb, 2004).…”

“…in the hippocampus following COC self-administration. The differential susceptibility to COC among these strains may be attributed to the impact of genetic background on both molecular and behavioral levels (Miguens et al, 2015). The role of reproductive status and the COC treatment on brain structure was also recorded in a study that investigated pregnant and virgin rats.…”