Manipulation of retinoic acid signaling in the nucleus accumbens shell alters rat emotional behavior

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 depr...

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Bibliographic Details
Published in:	Behavioural brain research Vol. 376; p. 112177
Main Authors:	Zhang, Yafang, Crofton, Elizabeth J., Smith, Tileena E.S., Koshy, Shyny, Li, Dingge, Green, Thomas A.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 30-12-2019
Subjects:	All-trans retinoic acid Anhedonia Animals Anxiety - metabolism Behavior, Animal - physiology Behavioral phenotyping Cold stress Depression - metabolism Elevated plus maze Emotions - physiology Eye Proteins - genetics Eye Proteins - metabolism Fatty Acid-Binding Proteins - genetics Fatty Acid-Binding Proteins - metabolism Forced swim test Gene Knockdown Techniques Locomotor activity Male Neophobia Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Nucleus Accumbens - metabolism Rats, Sprague-Dawley Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - metabolism Retinal Retinoic Acid 4-Hydroxylase - genetics Retinoic Acid 4-Hydroxylase - metabolism Retinoids Retinol Signal Transduction Social behavior Sucrose preference Tretinoin Tretinoin - metabolism Ventral striatum Vitamin A Forced swim test Elevated plus maze Anhedonia Retinoids Neophobia Behavioral phenotyping Retinol Vitamin A All-trans retinoic acid Social behavior Cold stress Sucrose preference Ventral striatum Retinal Locomotor activity Tretinoin
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Summary:	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.
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2019.112177