Abstract
Estradiol treatment of ovariectomized rodents is known to affect the morphology of dendritic spines and produce behavioral and cognitive effects. Kalirin-7 (Kal7), a PSD-localized Rho-guanine nucleotide exchange factor, is important for dendritic spine formation and stability. Male Kal7 knockout (Kal7KO) mice exhibit a number of abnormal behavioral and biochemical phenotypes. Given that chronic estradiol (E2) replacement of ovariectomized rats enhanced Kal7 expression in the hippocampus and in primary hippocampal cultures, we assessed the behavioral and biochemical effects of chronic E2 treatment of ovariectomized female wildtype and Kal7KO mice. Both intact and ovariectomized Kal7KO female mice exhibited decreased anxiety-like behavior compared to the corresponding wildtype in the elevated zero maze, unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the open field and enhanced performance in a passive avoidance fear conditioning task, which were both unaffected by genotype. Kal7KO female mice engaged in significantly more object exploration, both familiar and novel, than did wildtype females. E2 enhanced the acute locomotor response to cocaine, with no significant effect of genotype. Similar to Kal7KO males, Kal7KO females had decreased levels of NR2B in hippocampal post-synaptic density fractions, with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences.
- Received June 26, 2012.
- Revision received September 17, 2012.
- Accepted September 18, 2012.
- The American Society for Pharmacology and Experimental Therapeutics