scholarly journals Oxytocin receptors in the nucleus accumbens shell are necessary for the onset of maternal behavior in post-parturient mice

2020 ◽  
Author(s):  
Shannah Witchey ◽  
Heather K. Caldwell

AbstractOxytocin (Oxt) signaling via its receptor, the Oxt receptor (Oxtr), is important to the onset of mammalian maternal care. Specifically, evidence suggests that Oxt signaling around the time of parturition underlies the critical shift in how pups are perceived, i.e. from aversive stimuli to rewarding stimuli. Previous work from our lab has found that both Oxtr knockout (−/−) mice and forebrain-specific Oxtr knockout (FB/FB) are more likely than controls to abandon their first litters. Based on these data, we hypothesized that this observed pup abandonment phenotype was due to a failure of the brain to “switch” to a more maternal state. In order to identify where in the brain Oxt signaling contributes to the onset of maternal care we performed three experiments. In Experiment 1, virgin Oxtr FB/FB females were assessed for genotypic differences in maternal behavior and c-Fos expression following maternal sensitization was quantified. In Experiment 2, c-Fos expression was quantified in Oxtr −/− and Oxtr FB/FB females following parturition. In Experiment 3, based on our findings from Experiment 2, the Oxtr in the nucleus accumbens shell (NAcc) was genetically deleted in female Oxtr floxed mice (Oxtr Flox/Flox) mice using a Cre recombinase expressing adeno-associated virus. In Experiment 1, sensitized virgin Oxtr FB/FB females had significantly lower retrieval latencies on the first day of testing and reduced c-Fos expression in the dorsal lateral septum compared to controls. In Experiment 2, increased c-Fos expression was observed in the NAcc shell of both Oxtr −/− and Oxtr FB/FB dams as compared to controls. In Experiment 3, virally mediated knockout of the Oxtr in the NAcc shell completely disrupted the onset of maternal care. Thus, by genetically deleting Oxtr expression in the NAcc the pup abandonment phenotype previously observed in Oxtr −/− and Oxtr FB/FB dams was recreated. Taken together, these data suggest that in post-parturient mice, Oxtr expression in the NAcc shell is critical to the onset of maternal behavior.

2004 ◽  
Vol 32 (05) ◽  
pp. 795-806 ◽  
Author(s):  
Hye-Jung Lee ◽  
Bombi Lee ◽  
Sun-Hye Choi ◽  
Dae-Hyun Hahm ◽  
Mi-Rye Kim ◽  
...  

We have previously shown that electroacupuncture (EA) at Shaohai and Neiguan ( HT 3- PC 6) points significantly attenuated stress-induced peripheral responses, including increases in blood pressure, heart rate and plasma catecholamines. In this study, we examined the central effect of EA on the expression of c-fos, one of the immediate-early genes in the brain of rats subjected to immobilization stress. Immobilization stress (180 minutes) preferentially produced a significant increase in Fos-like immunoreactivity (FLI) in stress-relevant regions including the paraventricular hypothalamic nucleus (PVN), arcuate nucleus (ARN), supraoptic nucleus (SON), suprachiasmatic nucleus (SCN), medial amygdaloid nucleus (AMe), bed nucleus of the stria terminalis (BST), hippocampus, lateral septum (LS), nucleus accumbens, and the locus coeruleus (LC). EA (3 Hz, 0.2 ms rectangular pulses, 20 mA) at HT 3- PC 6 on the heart and pericardium channels for 30 minutes during stress, significantly attenuated stress-induced FLI in the parvocellular PVN, SON, SCN, AMe, LS and the LC. However, EA stimulations at HT 3- PC 6 had no effect on FLI in the magnocelluar PVN, ARN, BST or the hippocampus. EA stimulation at HT 3- PC 6 had a greater inhibitory effect on stress-induced FLI than that at TE 5- LI 11, the triple energizer and large intestine meridian, or non-acupoints. These results demonstrated that EA attenuated stress-induced c-fos expression in brain areas. These results suggest that decreased c-fos expression in hypothalamic and LC neurons, among stress-related areas, may reflect the integrative action of acupuncture in stress response.


Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 5095-5104 ◽  
Author(s):  
Simone L. Meddle ◽  
Valerie R. Bishop ◽  
Effimia Gkoumassi ◽  
Fred W. van Leeuwen ◽  
Alison J. Douglas

Oxytocin plays a pivotal role in rat parturition, acting within the brain to facilitate its own release in the supraoptic nucleus (SON) and paraventricular nucleus, and to stimulate maternal behavior. We investigated oxytocin receptor (OTR) expression and activation perinatally. Using a 35S-labeled riboprobe complementary to OTR mRNA, OTR expression was quantified in proestrus virgin, 21- and 22-day pregnant, parturient (90 min. from pup 1 birth), and postpartum (4–12 h from parturition) rats. Peak OTR mRNA expression was observed at parturition in the SON, brainstem regions, medial preoptic area (mPOA), bed nucleus of the stria terminalis (BnST), and olfactory bulbs, but there was no change in the paraventricular nucleus and lateral septum. OTR mRNA expression was increased on the day of expected parturition in the SON and brainstem, suggesting that oxytocin controls the pathway mediating input from uterine signals. Likewise, OTR mRNA expression was increased in the mPOA and BnST during labor/birth. In the olfactory bulbs and medial amygdala, parturition induced increased OTR mRNA expression compared with pre-parturition, reflecting their immediate response to new stimuli at birth. Postpartum OTR expression in all brain regions returned to levels observed in virgin rats. Parturition significantly increased the number of double-immunolabeled cells for Fos and OTR within the SON, brainstem, BnST, and mPOA regions compared with virgin rats. Thus, there are dynamic region-dependent changes in OTR-expressing cells at parturition. This altered OTR distribution pattern in the brain perinatally reflects the crucial role oxytocin plays in orchestrating both birth and maternal behavior.


2013 ◽  
Vol 16 (8) ◽  
pp. 1767-1780 ◽  
Author(s):  
Li-li Sun ◽  
Yan Zhang ◽  
Jian-feng Liu ◽  
Jun Wang ◽  
Wei-li Zhu ◽  
...  

Abstract Melanin-concentrating hormone (MCH) is a neuropeptide and its receptor is extensively expressed throughout the brain. MCH has been suggested to regulate the rewarding and reinforcing effects of psychostimulants by potentiating the dopaminergic system within the midbrain. Moreover, MCH and its receptor can regulate ERK activity. The present study investigated the role of MCH in the nucleus accumbens (NAc) in rats behaviourally sensitized to methamphetamine (Meth). We found that the development of Meth-induced locomotor sensitization was attenuated by MCH infused into the NAc shell but not core. Moreover, the elevation of ERK phosphorylation in the NAc shell induced by Meth was inhibited by locally infused MCH. Infusion of the MCH receptor 1 (MCHR1) antagonist SNAP 94847 into the NAc shell but not core augmented the initiation of locomotor sensitization and amplitude of elevated phosphorylated ERK levels induced by Meth. The expression of Meth-induced locomotor sensitization and ERK alterations after 1 wk withdrawal were not affected by either MCH or SNAP 94847 infused into the NAc shell or core. These results indicate that MCH in the NAc shell plays a critical role in the development but not expression of Meth-induced locomotor sensitization in rats, which might be mediated by the ERK signalling pathway. Our study suggests that MCH might be a potential target for the treatment of Meth addiction.


2018 ◽  
Vol 32 (8) ◽  
pp. 911-921 ◽  
Author(s):  
Kira-Elise Wilson ◽  
Sigrid Limburg ◽  
Melissa K Duggan ◽  
Adam J Lawther ◽  
Spencer J Williams ◽  
...  

Introduction: This study aimed to investigate the effects of the galanin-3 receptor antagonist, SNAP 37889, on c-Fos protein expression after cue-induced reinstatement of alcohol-seeking in the brains of alcohol-preferring rats. Methods: Eighteen alcohol-preferring rats were trained to self-administer 10% v/v ethanol in the presence of response-contingent cues, which was followed by extinction. Rats were then treated with SNAP 37889 (30 mg/kg, i.p.) or vehicle, before being tested for cue-induced reinstatement. Administration of SNAP 37889 reduced cue-induced reinstatement of ethanol-seeking behaviour. To examine the effect of SNAP 37889 and cue-induced reinstatement on neuronal activation, c-Fos expression was measured in subregions of the medial prefrontal cortex and nucleus accumbens. Results: SNAP 37889 administration increased c-Fos immunoreactivity in the nucleus accumbens shell, but was without effect in the nucleus accumbens core and the medial prefrontal cortex. Dual-label Fos/tyrosine hydroxylase immunohistochemistry was used to examine the effects of SNAP 37889 on dopamine neurons in the ventral tegmental area; however, no differences between SNAP 37889 and vehicle-treated rats were found. Conclusions: These data support previous findings of galanin-3 receptor involvement in cue-induced reinstatement of alcohol-seeking behaviour, and provide novel evidence that the ability of galanin-3 receptor antagonism to attenuate cue-induced reinstatement relates to activation of the nucleus accumbens shell.


Author(s):  
Xiaoluan Xia ◽  
Lingzhong Fan ◽  
Chen Cheng ◽  
Luqi Cheng ◽  
Long Cao ◽  
...  

AbstractTwo nucleus accumbens subregions, the shell and core, differ in the patterns whereby they integrate signals from prefrontal and limbic areas of the brain. In this study, we investigated whether the disproportionate volumetric differences of these brain areas, particularly the prefrontal cortex, between humans and macaques are accompanied by unique modifications of their macroscopic integrative connections with the shell and core. More specifically, we characterized the tractographic connectivity profiles of the human and macaque shell-core architecture and compared them between the two species. To make the cross-species comparisons more viable, we used the same whole-brain voxel-wise tractography-defined shell-like and core-like divisions in the two species as seeds and delineated pairs of interspecies connectionally comparable (ICC) target regions based on the similarity of the resting-state functional connectivity profiles for the two species, and finally used these seeds and ICC targets to establish a fingerprint-based common space for cross-species comparisons. Our results revealed that dissimilar structural connectivity profiles were found in the prefrontal but not the subcortical target group. We further localized this difference to specific targets to infer possible functional modifications between the two species.


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