Journal
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
Volume 8, Issue -, Pages -Publisher
FRONTIERS RESEARCH FOUNDATION
DOI: 10.3389/fnbeh.2014.00092
Keywords
T-type Ca2+ channels; anxiety; memory and learning; psychostimulants; drugs of abuse; spontaneous behavior
Categories
Funding
- Inserm
- ATIP-Avenir (Inserm)
- Sanofi-Aventis R and D
- Agence Nationale de la Recherche [ANR-2010-JCJC-1412]
- ANR [ANR-09-MNPS-037]
- AFM (AFM-PainT)
- FRM
- Labex ICST
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The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated (LVA) T-type calcium channels (Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Ca(v)3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty induced locomotor activity is unaffected. Deletion of the T-type channel Ca(v)3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Ca(v)3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations.
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