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L-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes.

TitleL-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes.
Publication TypeJournal Article
Year of Publication2016
AuthorsKabir ZD, Lee AS, Rajadhyaksha AM
JournalJ Physiol
Volume594
Issue20
Pagination5823-5837
Date Published2016 10 15
ISSN1469-7793
KeywordsAffect, Animals, Behavior, Addictive, Calcium Channels, L-Type, Cognition, Endophenotypes, Humans
Abstract

Brain Cav 1.2 and Cav 1.3 L-type Ca2+ channels play key physiological roles in various neuronal processes that contribute to brain function. Genetic studies have recently identified CACNA1C as a candidate risk gene for bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD) and autism spectrum disorder (ASD), and CACNA1D for BD and ASD, suggesting a contribution of Cav 1.2 and Cav 1.3 Ca2+ signalling to the pathophysiology of neuropsychiatric disorders. Once considered sole clinical entities, it is now clear that BD, SCZ, MDD and ASD share common phenotypic features, most likely due to overlapping neurocircuitry and common molecular mechanisms. A major future challenge lies in translating the human genetic findings to pathological mechanisms that are translatable back to the patient. One approach for tackling such a daunting scientific endeavour for complex behaviour-based neuropsychiatric disorders is to examine intermediate biological phenotypes in the context of endophenotypes within distinct behavioural domains. This will better allow us to integrate findings from genes to behaviour across species, and improve the chances of translating preclinical findings to clinical practice.

DOI10.1113/JP270673
Alternate JournalJ. Physiol. (Lond.)
PubMed ID26913808
PubMed Central IDPMC5063939
Grant ListF31 DA032169 / DA / NIDA NIH HHS / United States
R01 DA029122 / DA / NIDA NIH HHS / United States