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

Abstract

Neonatal handling has been shown to induce a short-term reduction in the binding properties of beta-adrenoceptors and in their primary biochemical responses in the young rat brain, which may account for the reduced responsiveness to stress observed in the handled rats. We have studied the persistence and duration of these changes in cerebral cortex, cerebellum and hippocampus at successive stages of life in neonatally handled rats. Binding properties of the beta-adrenoceptors in handled animals were essentially similar to those of the control rats from 3 to 24 months of age. However, handling disturbed the efficacy of the beta-adrenoceptor intracellular signalling since the isoprenaline-induced accumulation of cyclic AMP was reduced in cerebral cortex at 1, 12 and 24 months; in cerebellum at 12 and 18 months; and in hippocampus at 3 and 12 months. This effect might be partially dependent on a regulatory action of handling on the adenylyl cyclase enzyme itself since both basal and forskolin-induced accumulation of cyclic AMP were persistently reduced. Therefore, postnatal handling can be considered as an effective intervention that modifies sensitivity to various hormonal and neurochemical signals; these changes may be involved over a long period of time in protection against an excessive response to stress. These results suggest that the long-lasting adaptation of the adenylyl cyclase transduction system, which affects the primary biochemical response of the beta-adrenoceptor, may participate in the effects of this manipulation.

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.…”

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.…”

Early life handling decreases serotonin turnover in the nucleus accumbens and affects feeding behavior of adult rats

“…Knowing that quinpirole, a selective dopamine D2/D3 receptor agonist, decreases the preference for chocolate biscuits consumption in rats (Cooper & Al-Naser, 2006), it is possible that imipramine's action increasing D3 receptor expression in the nucleus accumbens of neonatally handled rats would therefore inhibit their natural preference for palatable food. Norepinephrine also plays an important role in the regulation of hunger and satiety (Wellman, 2000), and it is described that handling during early postnatal life influences central noradrenergic transmission (Baamonde et al, 1999(Baamonde et al, , 2002. While associated with sucrose sham-feeding (Hajnal & Norgren, 2004) and palatable food consumption (Fallon et al, 2007), the total amount of norepinephrine in the nucleus accumbens was measured in another study from our group (Silveira et al, 2009) and it was not different between neonatally handled and nonhandled animals in adulthood.…”