OBJECTIVES: The present study examines the cellular mechanisms by which scopolamine produces antidepressant-like effects through its action in the ventrolateral midbrain periaqueductal gray (vlPAG).
METHODS: We used a well-established mouse model of depression induced by chronic restraint stress (CRS) exposure for 14 days. Behaviors were tested using the forced swim test (FST), tail suspension test (TST), female urine sniffing test (FUST), novelty-suppressed feeding test (NSFT), and locomotor activity (LMA). Synaptic transmission in the vlPAG was measured by whole-cell patch-clamp recordings. IntravlPAG microinjection was used to pharmacologically verify the signaling cascades of scopolamine in the vlPAG.
RESULTS: The results demonstrated that intraperitoneal injection of scopolamine produced antidepressant-like effects in a dose-dependent manner without affecting locomotor activity. CRS elicited depression-like behaviors, whereas intraperitoneal injection of scopolamine alleviated CRS-induced depression-like behaviors. CRS diminished glutamatergic transmission in the vlPAG, while scopolamine reversed the above effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) antagonist CNQX prevented scopolamine-induced antidepressant-like effects.
CONCLUSIONS: Scopolamine ameliorated CRS-elicited depression-like behavior required activation of VDCC, resulting in activity-dependent release of brain-derived neurotrophic factor (BDNF), engaging the TrkB receptor and downstream mTORC1 signaling in the vlPAG.
MAIN BODY: We argue that broader consideration of lactation, incorporating evolutionary, comparative and anthropological aspects, could provide new insights into breastfeeding practices and problems, enhance research and ultimately help to develop novel approaches to improve initiation and maintenance. Our current focus on breastfeeding as a strategy to improve health outcomes must engage with the evolution of lactation as a flexible trait under selective pressure to maximise reproductive fitness. Poor understanding of the dynamic nature of breastfeeding may partly explain why some women are unwilling or unable to follow recommendations.
CONCLUSIONS: We identify three key implications for health professionals, researchers and policymakers. Firstly, breastfeeding is an adaptive process during which, as in other mammals, variability allows adaptation to ecological circumstances and reflects mothers' phenotypic variability. Since these factors vary within and between humans, the likelihood that a 'one size fits all' approach will be appropriate for all mother-infant dyads is counterintuitive; flexibility is expected. From an anthropological perspective, lactation is a period of tension between mother and offspring due to genetic 'conflicts of interest'. This may underlie common breastfeeding 'problems' including perceived milk insufficiency and problematic infant crying. Understanding this - and adopting a more flexible, individualised approach - may allow a more creative approach to solving these problems. Incorporating evolutionary concepts may enhance research investigating mother-infant signalling during breastfeeding; where possible, studies should be experimental to allow identification of causal effects and mechanisms. Finally, the importance of learned behaviour, social and cultural aspects of primate (especially human) lactation may partly explain why, in cultures where breastfeeding has lost cultural primacy, promotion starting in pregnancy may be ineffective. In such settings, educating children and young adults may be important to raise awareness and provide learning opportunities that may be essential in our species, as in other primates.
RESULTS: In addition to the Kinabatangan River, a known barrier for dispersal in tree shrews, the heterogeneous landscape along the riverbanks affected the genetic structure in this species. Specifically, while in larger connected forest fragments along the northern riverbank genetic connectivity was relatively undisturbed, patterns of genetic differentiation and the distribution of mitochondrial haplotypes in a local scale indicated reduced migration on the strongly fragmented southern riverside. Especially, oil palm plantations seem to negatively affect dispersal in T. longipes. Clear sex-biased dispersal was not detected based on relatedness, assignment tests, and haplotype diversity.
CONCLUSION: This study revealed the importance of landscape connectivity to maintain migration and gene flow between fragmented populations, and to ensure the long-term persistence of species in anthropogenically disturbed landscapes.