Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus
- 18 July 2006
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 24 (2) , 586-594
- https://doi.org/10.1111/j.1460-9568.2006.04924.x
Abstract
Recent observations indicate that drugs of abuse, including alcohol and opiates, impair adult neurogenesis in the hippocampus. We have studied in rats the impact of cocaine treatment (20 mg/kg, daily, i.p.) on cell proliferation, survival and maturation following short‐term (8‐day) and long‐term (24‐day) exposure. Using 5′‐bromo‐2‐deoxyuridine (BrdU) and Ki‐67 as mitotic markers at the end of the drug treatments, we found that both short‐ and long‐term cocaine exposures significantly reduced cell proliferation in the dentate gyrus (DG) of the hippocampus. By labelling mitotic cells with BrdU pulses before or during the early stages of the drug treatment, we determined that long‐term cocaine exposure did not affect the survival of newly generated cells. In register with this finding, cocaine chronic exposure did not increase the number of apoptotic cells labelled by TUNEL (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling). Using doublecortin (DCX) immunocytochemistry and electron microscopy, we next examined the effects of cocaine exposure on the maturation of the neural precursors and on synaptic output to CA3. DCX immunocytochemistry showed that immature hippocampal cells of rats exposed to cocaine displayed normal arborization patterns and similar degrees of colocalization with BrdU at two different developmental stages. Moreover, cocaine did not produce significant morphological alterations of the mossy fibre projection system to stratum lucidum in the CA3 area of the hippocampus. The results presented demonstrate that chronic cocaine exposure impairs proliferation dynamics in the DG without significantly altering either the survival and growth of immature cells or the structural features of terminal projections to CA3.Keywords
This publication has 46 references indexed in Scilit:
- Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse HippocampusJournal of Neuroscience, 2006
- Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neuronsEuropean Journal of Neuroscience, 2005
- Adult Neurogenesis: From Precursors to Network and PhysiologyPhysiological Reviews, 2005
- Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase‐67 expression and cell proliferation in the adult rat hippocampusEuropean Journal of Neuroscience, 2005
- Repetitive Cocaine Administration Decreases Neurogenesis in Adult Rat HippocampusAnnals of the New York Academy of Sciences, 2004
- Memory traces of trace memories: neurogenesis, synaptogenesis and awarenessTrends in Neurosciences, 2004
- For the Long RunNeuron, 2004
- Stress and Cocaine AddictionThe Journal of Pharmacology and Experimental Therapeutics, 2002
- Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampusJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 2000
- Addictive drugs as reinforcers: multiple partial actions on memory systemsAddiction, 1996