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

Addict Biol. 2017 Jan;22(1):78-92. doi: 10.1111/adb.12294. Epub 2015 Sep 2.

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.

Keywords: 3D neuron analysis; CA1; Fischer 344; Lewis; genetic background; intracellular injections.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Dendritic Spines / drug effects*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology*
  • Hippocampus / drug effects*
  • Male
  • Models, Animal
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Self Administration*
  • Species Specificity

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine