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Effects of Stathmin 1 Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress.

ABSTRACT: Stathmin (STMN), a microtubule-destabilizing factor, can regulate fear, anxiety, and learning. Social defeat stress (SDS) has detrimental effects on mental health and increases the risk of various psychiatric diseases. This study investigated the effects of STMN1 gene knockout (KO) on behavioral parameters and dopaminergic markers using an SDS mouse model. The STMN1 KO mice showed anxious hyperactivity, impaired object recognition, and decreased levels of neutral and social investigating behaviors at baseline compared to wild-type (WT) mice. The impact of SDS on neutral, social investigating and dominant behaviors differed markedly between the STMN1 WT and KO mice. In addition, different levels of total DARPP-32 and pDARPP-32 Thr75 expression were observed among the control, unsusceptible, and susceptible groups of STMN1 KO mice. Our results show that STMN1 has specific roles in locomotion, object recognition, and social interactions. Moreover, SDS had differential impacts on social interactions and dopaminergic markers between STMN1 WT and KO mice.

SUBMITTER: Nguyen TB

PROVIDER: S-EPMC6769668 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Effects of Stathmin 1 Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress.

Nguyen Thong Ba TB Prabhu Vishwanath Vasudev VV Piao Yan Hong YH Oh Young Eun YE Zahra Rami Fatima RF Chung Young-Chul YC

Brain sciences 20190826 9

Stathmin (STMN), a microtubule-destabilizing factor, can regulate fear, anxiety, and learning. Social defeat stress (SDS) has detrimental effects on mental health and increases the risk of various psychiatric diseases. This study investigated the effects of STMN1 gene knockout (KO) on behavioral parameters and dopaminergic markers using an SDS mouse model. The STMN1 KO mice showed anxious hyperactivity, impaired object recognition, and decreased levels of neutral and social ...[more]

PMID: 31454951

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Project description:RATIONALE:Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. OBJECTIVES:We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. METHODS:Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. RESULTS:Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. CONCLUSIONS:Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify how social defeat stress may alter the expression of extrahypothalamic CRF-R1 and glucocorticoid receptors.

Dataset Information

Effects of Stathmin 1 Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress.

Publications

Effects of <i>Stathmin 1</i> Gene Knockout on Behaviors and Dopaminergic Markers in Mice Exposed to Social Defeat Stress.

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