The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.
Early life stress interacts with adult stress to differentially modulate neural systems and vulnerability to various psychiatric illnesses. However, the effects of early life stress and adult stress on addictive behaviors have not been sufficiently investigated. We examined the effects of early life stress in the form of prolonged maternal separation followed in early adulthood by either 10 days of chronic variable stress or no stress on methamphetamine self-administration, extinction, and cue-induced reinstatement. We observed that chronic variable stress in adulthood reduced methamphetamine self-administration in rats with a history of early life stress. These findings add to an emerging body of literature suggesting interactions between and early life and early adulthood stressors on adult behavioral phenotypes.
Background: Breast cancer metastases generally occur in the lymph nodes, bone, lungs, or liver. Very rarely does a primary breast cancer metastasize to the colon, and even more rarely does the metastasis cause a large bowel obstruction. To our knowledge, there are no reports in the literature of the surgical management of elderly patients presenting with metastatic breast cancer as a large bowel obstruction. Here we present an unusual case of breast cancer metastasis of an elderly female, years after initial diagnosis and treatment of the primary breast cancer, that metastasized to the ascending colon and presented as a large bowel obstruction, ultimately treated with diverting ileostomy. The patient's rare presentation illustrates the necessity to consider metastatic breast cancer among patients with large bowel obstruction, and the consideration for palliation of symptoms with diversion.Case Description: The patient is an 84-year-old otherwise healthy female with history of right breast invasive lobular carcinoma, who underwent bilateral mastectomy, right axillary lymph node dissection, and adjuvant chemotherapy, radiation, and letrozole in 2017. In March of 2022, the patient presented with radiographic evidence of a proximal large bowel obstruction. On exploratory laparotomy she was found to have an ascending colon mass as well as widespread intra-abdominal carcinomatosis consistent with metastatic breast cancer. She underwent a diverting loop ileostomy for palliation of her obstructive symptoms and later followed with oncology for palliative chemotherapy and anti-hormone therapy. She overall recovered well without any future plans for surgical intervention.Conclusions: Although uncommon, it is important to consider metastatic disease when evaluating patients with history of breast cancer for large bowel obstruction. Failure to do so can result in a delay in recognition of metastatic tumor biology or even a misdiagnosis. This may impede appropriate treatment and may contribute to significant morbidity or even mortality for patients.
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