ORIGINAL PAPER Association Between Na + ,K + -ATPase Activity and the Vulnerability/Resilience to Mood Disorders induced by Early Life Experience Patrı ´cia Pelufo Silveira • Andre ´ Krumel Portella • Carla da Silva Benetti • Alexandra Ioppi Zugno • Emilene Barros da Silva Scherer • Cristiane Bastos Mattos • Angela T. S. Wyse • Aldo Bolten Lucion • Carla Dalmaz Received: 28 February 2011 / Accepted: 7 June 2011 / Published online: 22 June 2011 Ó Springer Science+Business Media, LLC 2011 Abstract There is increasing evidence that early life events can influence neurodevelopment and later suscepti- bility to disease. Chronic variable stress (CVS) has been used as a model of depression. The objective of this study was to evaluate the interaction between early experience and vulnerability to chronic variable stress in adulthood, analyzing emotional, metabolic and neurochemical aspects related to depression. Pups were (1) handled (10 min/day) or (2) left undisturbed from day 1 to 10 after birth. When the animals reached adulthood, the groups were subdivided and the rats were submitted or not to CVS, which consisted of daily exposure to different stressors for 40 days, followed by a period of behavioral tasks, biochemical (plasma cor- ticosterone and insulin sensitivity) and neurochemical (Na ? ,K ? -ATPase activity in hippocampus, amygdala and parietal cortex) measurements. Neonatally-handled rats demonstrated shorter immobility times in the forced swimming test, independently of the stress condition. There was no difference concerning basal corticosterone or insulin sensitivity between the groups. Na ? ,K ? -ATPase activity was decreased in hippocampus and increased in the amyg- dala of neonatally-handled rats. CVS decreased the enzyme activity in the three structures, mainly in the non-handled group. These findings suggest that early handling increases the ability to cope with chronic variable stress in adulthood, with animals showing less susceptibility to neurochemical features associated with depression, confirming the rele- vance of the precocious environment to vulnerability to psychiatric conditions in adulthood. Keywords Neonatal handling Á Depression Á Chronic stress Á Insulin sensitivity Á Na ? ,K ? -ATPase activity Á Forced swimming test Introduction During recent years, much research has been focused on early life events and their effects in adulthood. The asso- ciation between the poor quality of the fetal environment and an increased risk for cardiovascular disease [1–3] and depression [4, 5] is well known. These findings are often suggested to be mediated by the programming of the hypothalamus-pituitary-adrenal (HPA) axis activity [4–7]. This programming is very important because it seems to generate many behavioral and physiological phenotypes and induce susceptibility or resilience to disease. P. P. Silveira Á A. B. Lucion Á C. Dalmaz PPG Neurocie ˆncias, Instituto de Cie ˆncias Ba ´sicas da Sau ´de (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil P. P. Silveira (&) Departamento de Pediatria e Puericultura, FAMED- Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2350, Largo Eduardo Zaccaro Faraco, 90035-903, Rio Grande do Sul, Porto Alegre, Brazil e-mail: 00032386@ufrgs.br A. I. Zugno Á E. B. da Silva Scherer Á C. B. Mattos Á A. T. S. Wyse Á C. Dalmaz Departamento de Bioquı ´mica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil A. B. Lucion Departamento de Fisiologia, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil P. P. Silveira Á A. K. Portella Á C. da Silva Benetti Nu ´cleo de Estudos da Sau ´de da Crianc ¸a e do Adolescente (NESCA), Faculdade de Medicina, Hospital de Clı ´nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio, Rio Grande do Sul, Brazil 123 Neurochem Res (2011) 36:2075–2082 DOI 10.1007/s11064-011-0531-1