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Novel targets for depression and anxiety disorders are necessary for the development of more effective pharmacotherapeutics. Our previous study found that the retinoic acid (RA) signaling pathway is the signaling pathway most enhanced in the nucleus accumbens (NAc) shell, a region important for depression, anxiety, and addiction. Genetic manipulations of RA signaling in the NAc affecting addiction-related behavior prompted our study of the role of retinoic acid signaling in depression-related and anxiety-related behavior using in vivo RNA interference. Knockdown of the retinoic acid degradation enzyme cytochrome p450 family 26 subfamily b member 1 (Cyp26b1) in the nucleus accumbens shell increased depression-related behavior while decreasing anxiety-like behavior. Knockdown of the retinoic acid binding protein, cellular RA binding protein 2 (Crabp2), also increased depression-related behavior. Knockdown of another RA binding partner fatty acid binding protein 5 (Fabp5), did not alter these behaviors. These results further support the contention that RA signaling in the NAc shell can affect emotional behavior and that targeting some components of this pathway could be a promising avenue for developing novel treatments for depression and anxiety.
This article was published in the following journal.
Name: Behavioural brain research
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Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.
A cytochrome P450 enzyme that resides in the ENDOPLASMIC RETICULUM. It catalyzes the conversion of trans-RETINOIC ACID to 4-hydroxyretinoic acid.
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signalling pathways.
A composite structure of the TELENCEPHALON that is defined by connectivity. It includes the NUCLEUS ACCUMBENS; the ISLANDS OF CALLEJA; and parts of the CAUDATE NUCLEUS; the PUTAMEN; and the SUBSTANTIA INNOMINATA.
A cytochrome P450 enzyme family whose members function in the metabolism of RETINOIC ACID. It includes RETINOIC ACID 4-HYDROXYLASE.
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