Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis

Huiyuan Zheng; Linda Rinaman

doi:10.1111/ejn.12123

Solitary Nitric Oxide Signaling Mediates Mild Stress-Induced Anxiety and Norepinephrine Release in the Bed Nucleus of the Stria Terminalis during Protracted Ethanol Withdrawal

Behavioural Neurology ◽

10.1155/2021/2149371 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zhenglin Zhao ◽

Sang Chan Kim ◽

Yu Jiao ◽

Yefu Wang ◽

Bong Hyo Lee ◽

...

Keyword(s):

Nitric Oxide ◽

Elevated Plus Maze ◽

In Vivo Microdialysis ◽

Ethanol Withdrawal ◽

Mild Stress ◽

Stria Terminalis ◽

Bed Nucleus ◽

Nitric Oxide Signaling ◽

Plus Maze

Ethanol withdrawal (EtOHW) alters the pattern of neurohormonal and behavioral response toward internal and external stimuli, which mediates relapse to alcohol use even after a long period of abstinence. Increased noradrenergic signaling from the nucleus tractus solitarius (NTS) to the bed nucleus of the stria terminalis (BNST) during EtOHW underlies withdrawal-induced anxiety, while nitric oxide synthase (NOS) inhibitors injected into the periaqueductal area attenuate EtOHW-induced anxiety. Therefore, this study investigated the involvement of NOS within the NTS in anxiety and increased norepinephrine (NE) release in the BNST during protracted EtOHW in rats exposed to a mild stress. Rats were intraperitoneally administered 3 g/kg/day EtOH for 21 days followed by 28 days of withdrawal, and on the 28th day of withdrawal, the rats were subjected to restraint stress for 7 minutes. The elevated plus maze test was employed to evaluate anxiety-like behavior in rats, and in vivo microdialysis was used to measure the extracellular NE level in the BNST. In elevated plus maze tests, EtOHW rats but not EtOH-naive rats exhibited anxiety-like behavior when challenged with 7-minute mild restraint stress, which was, respectively, mitigated by prior intra-NTS infusion of the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or selective neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI). Each of these agents also decreased the plasma corticosterone levels in EtOHW rats. In in vivo microdialysis, prior intra-NTS infusion of carboxy-PTIO, L-NAME, or 7-NI attenuated the mild stress-induced NE release in the BNST of EtOHW rats. Additionally, EtOHW rats showed increased solitary nNOS gene and protein expression. Moreover, the anxiolytic effect of intra-NTS administration of 7-NI was abolished by subsequent intra-NTS administration of sodium nitroprusside. These results suggest that elevation of solitary nitric oxide signaling derived from nNOS mediates stress-precipitated anxiety and norepinephrine release in the BNST during protracted EtOHW.

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Yohimbine anxiogenesis in the elevated plus maze is disrupted by bilaterally disconnecting the bed nucleus of the stria terminalis from the central nucleus of the amygdala

Neuroscience ◽

10.1016/j.neuroscience.2012.08.008 ◽

2012 ◽

Vol 223 ◽

pp. 200-208 ◽

Cited By ~ 13

Author(s):

L. Cai ◽

H. Bakalli ◽

L. Rinaman

Keyword(s):

Elevated Plus Maze ◽

Central Nucleus ◽

Stria Terminalis ◽

Bed Nucleus ◽

Plus Maze

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Corticotropin-releasing factor infusion in the bed nucleus of the stria terminalis of lactating mice alters maternal care and induces behavioural phenotypes in offspring

Scientific Reports ◽

10.1038/s41598-020-77118-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kerstin Camile Creutzberg ◽

Érika Kestering-Ferreira ◽

Thiago Wendt Viola ◽

Luis Eduardo Wearick-Silva ◽

Rodrigo Orso ◽

...

Keyword(s):

Locomotor Activity ◽

Maternal Care ◽

Corticotropin Releasing Factor ◽

Maternal Behaviour ◽

Stria Terminalis ◽

Bed Nucleus ◽

Plus Maze ◽

Maternal Brain ◽

Nesting Material ◽

Peripartum Period

AbstractThe peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.

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Neuroanatomical pathways underlying the effects of hypothalamo-hypophysial-adrenal hormones on exploratory activity

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0075 ◽

2017 ◽

Vol 28 (6) ◽

pp. 617-648

Author(s):

Robert Lalonde ◽

Catherine Strazielle

Keyword(s):

Nucleus Accumbens ◽

Open Field ◽

Basolateral Amygdala ◽

Elevated Plus Maze ◽

Field Tests ◽

Lateral Septum ◽

Target Region ◽

Bed Nucleus ◽

Adrenal Hormones ◽

Plus Maze

AbstractWhen injected via the intracerebroventricular route, corticosterone-releasing hormone (CRH) reduced exploration in the elevated plus-maze, the center region of the open-field, and the large chamber in the defensive withdrawal test. The anxiogenic action of CRH in the elevated plus-maze also occurred when infused in the basolateral amygdala, ventral hippocampus, lateral septum, bed nucleus of the stria terminalis, nucleus accumbens, periaqueductal grey, and medial frontal cortex. The anxiogenic action of CRH in the defensive withdrawal test was reproduced when injected in the locus coeruleus, while the amygdala, hippocampus, lateral septum, nucleus accumbens, and lateral globus pallidus contribute to center zone exploration in the open-field. In addition to elevated plus-maze and open-field tests, the amygdala appears as a target region for CRH-mediated anxiety in the elevated T-maze. Thus, the amygdala is the principal brain region identified with these three tests, and further research must identify the neural circuits underlying this form of anxiety.

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Medullary noradrenergic neurons projecting to the bed nucleus of the stria terminalis express mRNA for the NMDA-NR1 receptor

Brain Research Bulletin ◽

10.1016/s0361-9230(00)00229-x ◽

2000 ◽

Vol 52 (3) ◽

pp. 163-169 ◽

Cited By ~ 41

Author(s):

M.I Forray ◽

K Gysling ◽

M.E Andrés ◽

G Bustos ◽

S Araneda

Keyword(s):

Stria Terminalis ◽

Noradrenergic Neurons ◽

Bed Nucleus

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Prenatal Exposure to Ketamine Leads to Anxiety-Like Behaviors and Dysfunction in Bed Nucleus of Stria Terminalis

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa002 ◽

2020 ◽

Vol 23 (3) ◽

pp. 181-191

Author(s):

Jing Sun ◽

Jianbang Lin ◽

Xiaolong Feng ◽

Zhonghua Lu ◽

Taian Liu ◽

...

Keyword(s):

Prenatal Exposure ◽

Neuron Activity ◽

Stria Terminalis ◽

General Anesthetic ◽

Behavioral Alterations ◽

Bed Nucleus ◽

Infant Exposure ◽

Elevated Plus Maze Test ◽

Plus Maze ◽

Pregnant Mice

Abstract Background Both the clinical and preclinical studies have suggested embryonic or infant exposure to ketamine, a general anesthetic, pose a great threat to the developing brain. However, it remains unclear how ketamine may contribute to the brain dysfunctions. Methods A mouse model of prenatal exposure to ketamine was generated by i.m. injection and continuous i.p. infusion of pregnant mice. Open field test and elevated plus maze test were used to analyze the behavioral alterations induced by ketamine. Immunostaining by c-Fos was used to map the neuron activity. Chemogenetic modulation of the neurons was used to rescue the abnormal neuron activity and behaviors. Results Here we show that mice prenatally exposed to ketamine displayed anxiety-like behaviors during adulthood, but not during puberty. C-Fos immunostaining identified abnormal neuronal activity in Bed Nucleus of the Stria Terminalis, the silencing of which by chemogenetics restores the anxiety-like behaviors. Conclusions Taken together, these results demonstrate a circuitry mechanism of ketamine-induced anxiety-like behaviors.

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