Spontaneous Novelty Seeking and Amphetamine-induced Conditioning and Sensitization in Adult Mice Evidence of Dissociation as a Function of Age at Weaning

Abstract

Individual differences in coping with novelty and in the response to psychoactive drugs have been related to early life events, such as the age of weaning. Outbred CD-1 mice underwent a precocious (postnatal day (pnd) Apart from the individual genetic background, individual differences in the seeking for novelty and in vulnerability to drug abuse may also be the consequence of critical experiences occurring early in life. There is indeed a growing literature investigating the effects of precocious manipulations upon brain and behavioral regulations in animal models (for a review, see Laviola and Terranova 1998). In this context, the gradual transition to nutritional and behavioral independence, which NO . 2 takes place at weaning, can well be seen as a centerpiece in development. This is a period of neural and behavioral organization, and hence a potential vulnerability of CNS structures can be hypothesized (Greenough et al. 1990). Moreover, whereas the date of weaning is fixed in most rodent studies around the end of the third postnatal week, weaning is a gradual phenomenon under natural conditions (Galef 1981). Individual differences in the process of separation from the mother might lead to hormonal and behavioral consequences that contribute to the natural variability of phenotypes (Cirulli et al. 1997).Experimental manipulation of weaning time in cats and rats has been shown to affect a wide range of facets of the adult behavioral repertoire: specifically, it has been suggested that pups may adaptively respond to precocious weaning by speeding up subsequent development (Bateson et al. 1990). Accordingly, when compared with a regular weaning group, animals weaned precociously show a number of behavioral (Martin and Bateson 1985;Terranova and Laviola 1995;Loggi et al. 1996;Terranova et al. 2000) and neurochemical (see e.g. Sharman et al. 1982;Mann and Sharman 1983) changes, which can be regarded as signs of advanced ontogeny. Conversely, it has been shown that weaning itself acts as a developmental stimulus for the expression and onset of functional control of a specific opioid receptor (delta subpopulation), and that a late weaning may delay such development (Muhammad and Kitchen 1993;Kitchen et al. 1994; see also Terranova and Laviola 2001). Dopaminergic CNS systems have been reported to undergo maturation during the pre-and post-weaning period (Rao et al. 1991;Teicher et al. 1995;Moll et al. 2000). The individual organization of this neurobehavioral system might hence be affected by an early or a delayed separation from the lactating dam. Indeed, age at weaning is reported to affect the development of the dopaminergic system as well as the response to dopaminergic drugs (Cirulli et al. 1997;Laviola & Dell'Omo 1997).It has been recently suggested that the activation of brain mesolimbic pathways, which are involved in reward-related phenomena and motivation (Robbins and Everitt 1996;Wise 1996), share a common neurobiological substrate with the active search of novelty and other natural rewarding sensati...

Maternal deprivation and the development of stereotypic behaviour

“…Fewer studies have examined the specific effects of weaning age, however some have found evidence suggestive of altered DA functioning or gross abnormalities of behavioural control. Thus, early weaned animals can be more sensitive to psychostimulant drugs and show enhanced psychostimulant-induced place-conditioning (Laviola and Dell'Omo, 1997;Adriani and Laviola, 2002). Furthermore, repetitive oral behaviours in very early weaned piglets are associated with decreases in the major metabolites of DA, and increased numbers of DA receptors in specific areas of the basal ganglia (Fry et al, 1981;Sharman et al, 1982;Mann and Sharman, 1983; see also Poletto et al, 2006 for a recent finding of changes in the expression of hippocampal genes involved in glucocorticoid regulation in very early separated piglets).…”

“…Furthermore, the loss of a parent during childhood in humans significantly increases the likelihood of developing major depression during adulthood (Brown and Harris, 1978;Agid et al, 1999). Several studies of laboratory rats and mice also indicate that early separated animals exhibit higher levels of fearfulness than normally separated individuals, shown by reduced entries into the open arms of an elevated plus maze (Kikusui et al, 2004;Kanari et al, 2005;Kikusui et al, 2005) and reduced spontaneous novelty seeking (Adriani and Laviola, 2002).…”

Early social experience influences the development of stereotypic behaviour in captive-born striped mice Rhabdomys

“…These, often initially latent, effects of early weaning suggest early but pervasive changes in motivational state or in the control of behaviour (Latham and Mason, 2008), although these changes have yet to be assessed directly. In contrast with the effects of premature weaning, delayed weaning is associated with greater exploration in adulthood (Adriani and Laviola, 2002) and, in certain rearing environments, with reduced anxiety and abnormal behaviour (stereotypic behaviour and barberingself-removal of hair, or removal of hair by a cagemate; Bechard et al, submitted for publication). Naturally occurring variations in maternal care (e.g.…”

The Meaning of Weaning: Influence of the Weaning Period on Behavioral Development in Mice

“…Amongst CD-1 mice weaned from dams at day 15 PN versus day 25 PN, day 15 PN weaned offspring were found to exhibit increased locomotor activity [Laviola and Dell'Omo, 1997;Laviola and Terranova, 1998] and altered social play behavior Laviola, 1995, 2001]. Fewer studies have focused on the neural correlates of these behavioral changes, though mice weaned at earlier time points have been shown to have lower levels of 5HT1B mRNA in the hippocampus [Nakamura et al, 2008], lower brain weights yet higher levels of myelin basic proteins altered glucocorticoid receptor (GR) mRNA expression , and an increased behavioral sensitivity to the actions of ␦ -opioid agonists [Terranova and Laviola, 2001] and of D -amphetamine sulfate [Adriani and Laviola, 2002].…”