Neonatal Handling Prevents the Effects of Phencyclidine in an Animal Model of Negative Symptoms of Schizophrenia

Tejedor-Real, P.; Sahagun, M.; Biguet, Nicole Faucon; Mallet, Jacques

doi:10.1016/j.biopsych.2006.08.033

Cited by 15 publications

(7 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Physical exercise as an intervention has been generally shown to be less efficacious as an intervention strategy than either enrichment or formal training, suggesting it might be less influential [62]. Handling during the early postnatal period has been previously reported to attenuate stress effects [63, 64]. While early handling (weighing and culling of litters) was comparable in EM and NEM offspring, differences could certainly reflect the more sustained handling of EM animals as a component of behavioral testing.…”

Section: Discussionmentioning

confidence: 99%

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/−stress-related modifications to these trajectories

Cory‐Slechta

Virgolini

Rossi-George

et al. 2009

Behavioural Brain Research

View full text Add to dashboard Cite

This study sought to further understand how environmental conditions influence the outcomes of early developmental insults. It compared changes in monoamine levels in frontal cortex, nucleus accumbens and striatum of male and female Long-Evans rat offspring subjected to maternal Pb exposure (0, 50 or 150 ppm in drinking water from 2 mos pre-breeding until pup weaning) +/− prenatal (PS) (restraint on GD16-17) or PS + offspring stress (OS; 3 variable stress challenges to young adults) determined at 2 mos of age and at 6 mos of age in littermates subsequently exposed either to experimental manipulations (EM: daily handling and performance on an operant fixed interval (FI) schedule of food reward), or to no experience (NEM; time alone). Time alone (NEM conditions), even in normal (control) animals, modified the trajectory of neurochemical changes between 2 and 6 mos across brain regions and monoamines. EM significantly modified the NEM trajectories, and except NE and striatal DA, which increased, blunted the changes in monoamine levels that occurred over time alone. Pb+/stress modified the trajectory of monoamine changes in both EM and NEM conditions, but these predominated under NEM conditions. Stress-associated modifications, occurring mainly with NEM OS groups, were fully reversed by EM procedures, while reversals of Pb+/-stress-associated modifications occurred primarily in nucleus accumbens, a region critical to mediation of FI response rates. These results extend the known environmental conditions that modify developmental Pb+/-stress insults, which is critical to ultimately understanding whether early insults lead to adaptive or maladaptive behavior and to devising behavioral therapeutic strategies. That time alone and a set of EM conditions typically used as outcome measures in intervention studies can themselves invoke neurochemical changes, moreover, has significant implications for experimental design of such studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/−stress-related modifications to these trajectories

Cory‐Slechta

Virgolini

Rossi-George

et al. 2009

Behavioural Brain Research

View full text Add to dashboard Cite

show abstract

“…Stress-attenuating effects of handling during the early postnatal period have been documented (Cirulli et al, 2007; Tejedor-Real et al, 2007). In this study, however, no systematic early handling was carried out, and what early handling did occur was comparable in FI and NFI offspring.…”

Section: Discussionmentioning

confidence: 99%

Influence of low level maternal Pb exposure and prenatal stress on offspring stress challenge responsivity

et al. 2008

View full text Add to dashboard Cite

We previously demonstrated potentiated effects of maternal Pb exposure producing blood Pb(PbB) levels averaging 39 μg/dl combined with prenatal restraint stress (PS) on stress challenge responsivity of female offspring as adults. The present study sought to determine if: 1) such interactions occurred at lower PbBs, 2) exhibited gender specificity, and 3) corticosterone and neurochemical changes contributed to behavioral outcomes. Rat dams were exposed to 0, 50 or 150 ppm Pb acetate drinking water solutions from 2 mos prior to breeding through lactation (pup exposure ended at weaning; mean PbBs of dams at weaning were <1, 11 and 31 μg/dl, respectively); a subset in each Pb group underwent prenatal restraint stress (PS) on gestational days 16-17. The effects of variable intermittent stress challenge (restraint, cold, novelty) on Fixed Interval (FI) schedule controlled behavior and corticosterone were examined in offspring when they were adults. Corticosterone changes were also measured in non-behaviorally tested (NFI) littermates. PS alone was associated with FI rate suppression in females and FI rate enhancement in males; Pb exposure blunted these effects in both genders, particularly following restraint stress. PS alone produced modest corticosterone elevation following restraint stress in adult females, but robust enhancements in males following all challenges. Pb exposure blunted these corticosterone changes in females, but further enhanced levels in males. Pb-associated changes showed linear concentration dependence in females, but non-linearity in males, with stronger or selective changes at 50 ppm. Statistically, FI performance was associated with corticosterone changes in females, but with frontal cortical dopaminergic and serotonergic changes in males. Corticosterone changes differed markedly in FI vs. NFI groups in both genders, demonstrating a critical role for behavioral history and raising caution about extrapolating biochemical markers across such conditions. These findings demonstrate that maternal Pb interacts with prenatal stress to further modify both behavioral and corticosterone responses to stress challenge, thereby suggesting that studies of Pb in isolation from other disease risk factors will not reveal the extent of its adverse effects. These findings also underscore the critical need to extend screening programs for elevated Pb exposure, now restricted to young children, to pregnant, at risk, women.

show abstract

“…Handling also reverses negative effects induced in other animal models of early-life stress and schizophrenia (Francis et al, 2002, Tejedor-Real et al, 2007). Handling has, consequently, been viewed as a reciprocal treatment for early-life stress (for review see Laviola et al, 2008).…”

mentioning

confidence: 82%

Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats

et al. 2010

View full text Add to dashboard Cite

Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced increases in endocannabinoid content (piriform cortex), compared to group-reared rats. Our findings suggest alterations in the endocannabinoid system may contribute to the abnormal isolate phenotype. Handling modifies the endocannabinoid system and behavioral reactivity to context, but surmounts only some effects of social isolation. These data implicate a pivotal role for the endocannabinoid system in stress adaptation and emotionality-related disturbances.

show abstract

Neonatal Handling Prevents the Effects of Phencyclidine in an Animal Model of Negative Symptoms of Schizophrenia

Cited by 15 publications

References 83 publications

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/−stress-related modifications to these trajectories

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/−stress-related modifications to these trajectories

Influence of low level maternal Pb exposure and prenatal stress on offspring stress challenge responsivity

Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats

Contact Info

Product

Resources

About