Cellular mechanisms underlying the effects of an early experience on cognitive abilities and affective states (Fragment)

Efstathios Garoflos†, Theofanis Panagiotaropoulos†, Stavroula Pondiki†, Antonios Stamatakis†, Eleni Philippidis and Fotini Stylianopoulou*


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.
Method: 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.
Conclusion: 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.


It is generally accepted that early experiences have profound influences on brain development and thus on adult brain function and behavior. However the neurobiological mechanisms involved still remain elusive. An animal model employed in experiments aiming to elucidate such mechanisms is «neonatal handling» [1]. This manipulation alters hypothalamic-pituitary-adrenal (HPA) axis function and the ability of the organism to respond to stressful stimuli [1]. Thus, as adults, neonatally handled rats are less emotionally reactive, synthesize and secrete less corticotropin-releasing factor, adrenocorticotropin hormone (ACTH) and corticosterone following a variety of stressors [2], and their stress-induced secretion is more short-lived [3]. These differences in HPA axis reactivity have been attributed to an enhanced sensitivity of the negative-feedback loop [2], due to a handling-induced increase in the number of type II glucocorticoid receptors (GR) in the hippocampus [2].