Short-Term Effects of Postnatal Manipulation on Central β-Adrenoceptor Transmission

Abstract

Neonatal handling is known to induce long-lasting changes in behavioral and neuroendocrine responses to stress. Since the central noradrenergic system participates in the adaptive responses to stressful conditions we have analyzed the effects of postnatal handling on beta-adrenoceptor binding sites and isoprenaline- and forskolin-stimulated cyclic AMP accumulation in cerebral cortex, hippocampus and cerebellum of rats at 1 and 3 months of age. Handled animals showed reduced emotional reactivity and lower ACTH and corticosterone secretion after stress. Binding studies using [(3) H]CGP12-177 revealed increased beta-adrenoceptor binding sites in handled rats in cerebellum and cerebral cortex with no changes in hippocampus, and decreased affinity in all cerebral regions. Handling reduced basal levels of cyclic AMP in hippocampus and cerebellum but not in cerebral cortex. The concentration-response curves of cyclic AMP to isoprenaline were displaced to the right in cerebellum of handled rats without differences in Emax; however, Emax was significantly reduced in cerebral cortex and hippocampus. Direct stimulation of the catalytic subunit of adenylyl cyclase by forskolin reduced the efficiency in hippocampus and cerebellum, but not in cerebral cortex of handled animals. It is concluded that neonatal handling reduces the binding properties of beta-adrenoceptor and its primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress attained in the handled rats, and may explain the persistence of the effect. The present study emphasizes the role of the central noradrenergic system in modulating the behavioral and neurendocrine responses to neonatal handling.

G-Protein-Associated Signal Transduction Processes Are Restored after Postweaning Environmental Enrichment in Ts65Dn, a Down Syndrome Mouse Model

“…This effect is comparable to those previously reported in rats, where environmental stimulation produced long-lasting reduction of central noradrenergic responsiveness [67], and postnatal handling induced short- and long-lasting depression of AC functioning [42,43]. This may be explained since EE, when provided early in the life of normal animals, may also serve as a factor capable of moderating stressing responses, thus enabling the animals to cope more properly with learning challenges.…”

“…Our previous work suggested that the long-lasting adaptation of the AC transduction system was a key element in the effects of neonatal handling in rats [42,43,44], and clear alterations of AC and PLC signaling systems in DS brains. We here aimed to assess the possible changes in G protein signaling systems upon postweaning EE in Ts65Dn mice.…”

Postnatal Handling Induces Long-term Modifications in Central β-noradrenergic Signalling in Rats

“…We have previously shown that postnatal handling can differentially modify the binding properties of the badrenoceptor and its primary biochemical response in the young rat brain (Baamonde et al, 1999), emphasizing the role of the central noradrenergic system in the modulation of the behavioural and neuroendocrine responses to postnatal handling. Noradrenaline is involved in the control of emotions and in the reactivity to stressful conditions.…”

Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reaction

“…Elevated NA activity enhances anxiety-like behavioral responses and inappropriate activation of the locus coreuleus (LC), may participate in the exaggerated stimulus-responsiveness and increased emotionality seen in patients with stress or anxiety disorders (Priolo et al, 1991;Aston-Jones et al, 1996;Goddard and Charney, 1997). On the other hand, antidepressant treatment, that is effective in panic disorder patients, decreases LC firing and tyrosine hydroxylase (TH, rate-limiting enzyme in the synthesis of catecholamines) expression (Smith et al, 1995), and behavioral manipulations that decrease stress, such as postnatal handling modulate the responses of the noradrenergic system (Escorihuela et al, 1995a,b;Baamonde et al, 1999Baamonde et al, , 2002.…”