The genetic versus pharmacological invalidation of the cannabinoid CB(1) receptor results in differential effects on 'non-associative' memory and forebrain monoamine concentrations in mice

The endocannabinoid CB(1) receptor has been implicated in the inhibitory control of learning and memory. In the present experiment, we compared the behavioral response of CB(1) receptor knockout mice (CB(1)R(-/-)) with animals administered CB(1) receptor antagonist/inverse agonist SR141716A (rimonabant; 3 mg/kg IP, 30 min pre-trial) in terms of acquisition and retention of a habituation task and changes in cerebral monoamines. The results can be summarized as follows: (i) the acute and chronic invalidation of the CB(1) receptor resulted in an increase of behavioral habituation during the first exposure to an open field, indicative of enhanced acquisition of the task; (ii) CB(1)R(-/-) mice, but not rimonabant-treated animals, showed enhanced retention of the habituation task when re-tested 48 h and 1 week subsequent to the first exposure to the open field, respectively; (iii) the facilitation of retention of the habituation task in CB(1)R(-/-) mice was accompanied by a selective and site-specific increase in serotonin activity in hippocampus; and (iv) rimonabant-treated animals displayed 'antidepressant-like' neurochemical alterations of cerebral monoamines, that is, most parameters of monoaminergic activity were increased especially in dorsal striatum and hippocampus. Taken together, the present findings demonstrate that the genetic disruption of the CB(1) receptor gene can cause an improvement of behavioral habituation, which is considered to represent a form of 'non-associative' learning. Furthermore, our data support the assumption of a rimonabant-sensitive cannabinoid receptive site that is different from the 'classical' CB(1) receptor and which, under physiological conditions, might be involved in the inhibitory control of the acquisition but not retention of non-associative learning tasks.     

Memory impairments and hippocampal modifications in adult rats with neonatal isolation stress experience

Early life events have profound consequences. Our research demonstrates that the early life stress of neonatal isolation (1-h individual isolation on postnatal days 2-9) in rats has immediate and enduring neural and behavioral effects. Recently, we showed neonatal isolation impaired hippocampal-dependent context conditioned fear in adult rats. We now expand upon this finding to test whether neonatal isolation impairs performance in inhibitory avoidance and in the non-aversive, hippocampal-dependent object recognition task. In addition to assessments of hippocampal-dependent memory, we examined if neonatal isolation results in cellular alterations in the adult hippocampus. This was measured with antibodies that selectively label calpain-mediated spectrin breakdown product (BDP), a marker of cytoskeletal modification that can have neuronal consequences. Neonatally isolated male and female rats showed impaired performance in both memory tasks as well as elevated BDP levels in hippocampal immunoblot samples. In tissue sections stained for BDP, the cytoskeletal fragmentation was localized to pyramidal neurons and their proximal dendrites. Interestingly, the hippocampal samples also exhibited reduced staining for the postsynaptic marker, GluR1. Neonatal isolation may render those neurons involved in memory encoding to be vulnerable to calpain deregulation and synaptic compromise as shown previously with brain injury. Together with our prior research showing enhanced striatal-dependent learning and neurochemical responsivity, these results indicate that the early experience of neonatal isolation causes enduring yet opposing region-specific neural and behavioral alterations.     

Intergenerational predictors of diurnal cortisol secretion in early childhood

The present study examined potential intergenerational links that may contribute to atypical patterns of diurnal cortisol secretion in early childhood. Salivary cortisol samples were collected across 1 waking day in 36 pre‐school children whose mothers are participants in an ongoing longitudinal project. Hierarchical Linear Modeling (HLM) identified statistically significant predictors of individual differences in daily cortisol trajectories. Children displayed relatively low post‐awakening values and flatter cortisol trajectories across the day as a function of unsupportive maternal behaviour, second‐hand smoke and maternal histories of social withdrawal in childhood. These results suggest that individual differences in young children's pattern of diurnal cortisol are associated with a variety of current and historical maternal characteristics and behaviours. The identification of intergenerational predictors of children's diurnal neuroendocrine functioning may provide new insights into the transfer of health and developmental risk from parent to child. Copyright © 2007 John Wiley & Sons, Ltd.     

Adult attunement and child availability: Interaction of mother and caregiver with three‐year‐old kibbutz children

Relationships of mother and nonmaternal caregiver with 33 three‐year‐old kibbutz toddlers were investigated. Attunement and intrusiveness of these caregivers in their contact with children were determined by analysis of discrete child–adult interactions rather than by a global assessment of their relationships. The validity of these adult attunement scores was examined first by comparison of the attunement and intrusiveness scores of mother and of caregiver, and second by determining their association with independent scores of child availability to each of these caregiving adults. Results tended to support the validity of the present measures of adult attunement to the child. They indicated that in cases of disagreement mothers were more attuned than nonmaternal caregivers to the signals of the child, and the level of adult attuned agreement to the child was positively associated with cooperative attempts of children to involve caregivers in their activities © 2000 Michigan Association for Infant Mental Health.