Cellular mechanisms underlying the effects of an early experience on cognitive abilities and affective states.
In the present study we investigated the effects of neonatal handling, an animal model of early experience, on spatial learning and memory, on hippocampal glucocorticoid (GR), mineralocorticoid (MR) and type 1A serotonin (5-HT1A) receptors, as well as brain derived neurotrophic factor (BDNF), and on circulating leptin levels, of male rats.


METHODS
Spatial learning and memory following an acute restraint stress (30 min) were assessed in the Morris water maze. Hippocampal GR, MR and BDNF levels were determined immunocytochemically. 5-HT1A receptors were quantified by in vitro binding autoradiography. Circulating leptin levels, following a chronic forced swimming stress, were measured by radioimmunoassay (RIA). Data were statistically analyzed by analysis of variance (ANOVA).


RESULTS
Neonatal handling increased the ability of male rats for spatial learning and memory. It also resulted in increased GR/MR ratio, BDNF and 5-HT1A receptor levels in the hippocampus. Furthermore, leptin levels, body weight and food consumption during chronic forced swimming stress were reduced as a result of handling.


CONCLUSIONS
Neonatal handling is shown to have a beneficial effect in the males, improving their cognitive abilities. This effect on behavior could be mediated by the handling-induced increase in hippocampal GR/MR ratio and BDNF levels. The handling-induced changes in BDNF and 5-HT1A receptors could underlie the previously documented effect of handling in preventing "depression". Furthermore, handling is shown to prevent other maladaptive states such as stress-induced hyperphagia, obesity and resistance to leptin.
Garoflos
Efstathios
E
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.
Panagiotaropoulos
Theofanis
T
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.
Pondiki
Stavroula
S
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.
Stamatakis
Antonios
A
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.
Philippidis
Eleni
E
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.
Stylianopoulou
Fotini
F
Lab. Biology-Biochemistry, Dept. Basic Sciences, Faculty of Nursing, University of Athens, Papadiamantopoulou 123, 115 27 Athens, Greece.