Abstract
Different models of rodent maternal separation (MS) have been used to investigate long-term neurobiological and behavioral changes, associated with early stress. However, few studies have involved the analysis of sex-related differences in central anxiety modulation. This study investigated whether MS during breastfeeding affected adult males and females in terms of anxiety and brain GABA-A receptor-alpha-subunit immunoreactivity. The brain areas analyzed were the amygdale (AM), hippocampus (HP), medial prefrontal cortex (mPFC), medial preoptic area (POA) and paraventricular nucleus (PVN). Rats were housed under a reversed light/dark cycle (lights off at 7∶00 h) with access to water and food ad libitum. Animals underwent MS twice daily during the dark cycle from postnatal day 1 to postnatal day 21. Behavior was tested when rats were 65–70 days old using the elevated plus maze and after brains were treated for immunohistochemistry. We found that separated females spent more time in the open arms and showed more head dipping behavior compared with controls. The separated males spent more time in the center of the maze and engaged in more stretching behavior than the controls. Immunohistochemistry showed that separated females had less immunostained cells in the HP, mPFC, PVN and POA, while separated males had fewer immunolabeled cells in the PFC, PVN and AM. These results could indicate that MS has gender-specific effects on anxiety behaviors and that these effects are likely related to developmental alterations involving GABA-A neurotransmission.
Highlights
Adverse experiences have been proposed as having long lasting deleterious effects on shaping brain networks and behavioral development in mammals [1,2,3,4]
Mammals need care of their mothers to supply them with warmth, food, sensorial stimulation, endocrine regulation, and modulated emotional arousal; separation from mothers, cause high stress and when this stress is recurring during breastfeeding period, may carry to deleterious effects on behavior and neuroendocrine development
The results are not conclusive; some studies have found that animals subjected to Maternal Separation (MS) show increased anxiety-like behavior and related neuroendocrine alterations [10,11,12]; while other researchers have not reported such alterations [13] or have shown a reduction in anxiety in females but not in males [14,15]
Summary
Adverse experiences have been proposed as having long lasting deleterious effects on shaping brain networks and behavioral development in mammals [1,2,3,4]. Children who have experienced prolonged maltreatment, abuse or neglect rearing, use to have an increased risk of developing psychopathology like anxiety disorders, depression, attention deficit [5], learning problems and so on They are more likely to show heightened neuroendocrine responsiveness to stress, brain morphology changes, and neurochemical and gene expression patterns in the central nervous system related to the emergence of several psychopathologies [6,7,8]. In this sense, Maternal Separation (MS) is one of the paradigms to experimentally study the endocrine, behavioral and brain structural consequences of early life stress in animal models [9,3]. The results are not conclusive; some studies have found that animals subjected to MS show increased anxiety-like behavior and related neuroendocrine alterations [10,11,12]; while other researchers have not reported such alterations [13] or have shown a reduction in anxiety in females but not in males [14,15]
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