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Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice (Jonathan Epp)

AUTHORS: M. L. Mustroph, J. R. Merritt, A. L. Holloway, H. Pinardo, D. S. Miller, C. N. Kilby, P. Bucko, A. Wyer and J. S. Rhodes

ABSTRACT: Recent evidence suggests that wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesised to enhance plasticity  and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin–thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without  running wheels for 32 days. Half of the mice were fed chow containing valganciclovir to induce apoptosis in newly divided  neurons, and the other half were fed standard chow. For the first 10 days, mice received daily injections of bromodeoxyuridine  (BrdU) to label dividing cells. On the last 4 days, mice were tested for CPP, and then euthanized for measurement of adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in the dentate gyrus. Levels of running were similar  in mice fed valganciclovir-containing chow and normal chow. Valganciclovir significantly reduced the numbers of neurons  (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary mice and runner mice. Valganciclovir-fed runner mice

showed similar levels of neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed runner mice showed the  same abolishment of CPP as runner mice with intact neurogenesis. The results demonstrate that elevated adult hippocampal  neurogenesis resulting from running is not necessary for running to abolish cocaine CPP in mice.