Effects of amphetamine, dexfenfluramine, diazepam, and other pharmacological and dietary manipulations on food "seeking" and "taking" behavior in non-human primates

RATIONALE: Feeding consists of appetitive or foraging behavior followed by consummatory behavior. OBJECTIVES: To determine if pharmacological manipulations can differentially affect appetitive and consummatory aspects of food intake, and to compare these results to those obtained using naturalistic dietary manipulations. METHODS: Responding of baboons was studied using a schedule of reinforcement that simulated food "seeking" and food "taking." Responding during the seeking component was reinforced by stimuli paired with food, while responding during the taking component was reinforced with food. The effects of intramuscular amphetamine (AMPH), dexfenfluramine (DFEN), diethylpropion (DEP), phencyclidine (PCP), diazepam (DZP), as well as caloric prefeeding and acute food deprivation were determined. RESULTS: AMPH decreased food taking and increased food seeking, DEP decreased food taking without affecting food seeking, DFEN and PCP decreased both food taking and food seeking, while DZP increased both food taking and food seeking. Caloric prefeeding decreased food taking and increased food seeking, i.e., resembled AMPH, while acute deprivation increased both food taking and food seeking, i.e., resembled DZP. CONCLUSIONS: Manipulations that increase dopamine turnover, such as AMPH, increase food seeking, while decreasing food intake. In contrast, manipulations that increase serotonin turnover, such as DFEN, decrease both food seeking and food taking.     

Deprivation and mortality: the implications of spatial autocorrelation for health resources allocation

This paper aims at investigating whether the relationship between mortality and socio-economic deprivation is affected by the spatial autocorrelation of ecological data. A simple model is used in which mortality (all-ages and premature) is the dependent variable, and deprivation, morbidity and other socio-economic indicators are the explanatory variables. Deprivation is measured by the Townsend index; the other socio-economic variables are the median income, unequal income distribution (Gini coefficient) and population density. Morbidity is estimated on the basis of hospital admission rates and overweight prevalence. Spatial autocorrelation is measured by the Moran's I coefficient. All mortality and morbidity variables have significant, positive, and moderate-to-high spatial autocorrelation. Two multivariate models are explored: a weighted least-squares model ignoring spatial autocorrelation and a simultaneous autoregressive model. The paper concludes that spatial autocorrelation has a significant impact on the relationship between mortality and socio-economic variables. Future ecological models intended to inform health resources allocation need to pay greater attention to the spatial dimension of the data used.     

Shorter Axial Length and Increased Astigmatic Refractive Error are Associated With Socio-Economic Deprivation in an Adult UK Cohort

Purpose: To evaluate whether socio-economic deprivation is associated with ocular axial length and refractive error in a British cohort.

Methods: The study population consisted of 7,652 individuals who provided data to the prospective cataract database at Portsmouth Eye unit, UK over a 4 year period (January 2004 to June 2008). Indices of multiple deprivation (IMD) scores measuring both social and economic domains for each patient’s locality were calculated. The association of these measures of deprivation with axial length and refractive error (astigmatic and spherical) were evaluated using regression analyses after adjusting for age and sex.

Results: Socio-economically deprived areas (higher IMD scores) were inversely associated with axial lengths and astigmatic refraction. After controlling for age and sex, an inverse linear association was observed between axial length and IMD scores (-0.24mm in highest quintile compared to lowest; 95% confidence intervals: -0.33 to -0.15) and between astigmatic refraction and IMD scores (-0.12 dioptres in highest quintile compared to lowest; 95% confidence intervals: -0.21 to -0.03). There was no association between spherical refraction and IMD scores.

Conclusions: Axial length and astigmatic refraction were inversely associated with socio-economic deprivation in this population. Identification of the environmental exposures involved may identify reversible risk factors for impaired vision.     

On the evolution of attachment-disordered behaviour

Using an example of a goose which grew up in complete isolation, this article shows how escape behaviour increases through all its developmental steps by lack of a sufficient secure primary attachment object. If a gosling has no mother, its fear influences wide parts of its behaviour and blocks the capacity to approach another animal in order to form a new attachment. But the urge for attachment is still alive and provokes strong conflicts between this urge and fear. In these situations displacement activities and apathy occur – attachment-disordered behaviour. Under partly artificial circumstances, a change to ‘normal’ attachment behaviour took place by reduction of escape motivation, which enabled the goose to accept her brood. From this moment on the attachment-disordered behaviour, the displacement activity and the apathy disappeared. Implications to human behaviour are drawn – a comparison between displacement activity and neurotic symptoms, the state of apathy and personal disorder. A synthesis of ethological and psychoanalytical models concerning etiological and therapeutic aspects is discussed. Fear and attachment, not aggression and sexuality – our ‘animal heritage’ – are the primary factors which influence our development. The balance of fear and attachment is the basis for a healthy or unhealthy development of social relationships. This applies to social living animals as well as to humans.     

Impairment of experience-dependent cortical plasticity in aged mice

This study addresses the relationship between aging and experience-dependent plasticity in the mouse somatosensory cortex. Plasticity in the cortical representation of vibrissae (whiskers) was investigated in young (3 months), mature (14 months) and old (2 years) mice using [14C]2-deoxyglucose (2-DG) autoradiography. Plastic changes were evoked using two experimental paradigms. The deprivation-based protocol included unilateral deprivation of all but one row of whiskers for a week. In the conditioning protocol the animals were subjected to classical conditioning, where tactile stimulation of one row of whiskers was paired with an aversive stimulus. Both procedures evoked functional plasticity in the young group, expressed as a widening of the functional cortical representation of the spared or conditioned row. Aging had a differential effect on these two forms of plasticity. Conditioning-related plasticity was more vulnerable to aging: the plastic change was not detectable in mature animals, even though they acquired the behavioral response. Deprivation-induced plasticity also declined with age, but some effects were persistent in the oldest animals.     

Methylmercury-induced IL-6 release requires phospholipase C activities

Previous studies have reported that intrahemispheric connections between area 17 (V1, striate cortex) and other cortical visual areas are not point-to-point, but instead have some degree of convergence and divergence. Many pathological conditions can interfere with the normal development of patterns of cortico-cortical connections, but there is little information regarding whether or not early pathological insults can also induce permanent changes in the convergence and divergence of cortical connections. Obtaining this information is important because loss of precision in neural projections can contribute to functional deficits and behavioral impairment. In the present study we investigated whether retinal input is required for the development of normal values of convergence and divergence in the visual callosal pathway. We found that enucleation performed at birth induced significant increases in convergence and divergence compared to control animals. In contrast, values of convergence and divergence in rats enucleated at postnatal day 7 (P7) were similar to those in controls. Previous studies have shown that retinal input during the first postnatal week is required for the specification of the overall distribution and internal topography of visual callosal pathways. Our present results therefore extend these previous finding by showing that retinal input during the first postnatal week also specifies the precision of cortico-cortical projections. These findings raise the possibility that the precision of neural connections may be reduced in other pathological conditions that affect early development of neural connections.     

Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats

BACKGROUND: There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety. METHODS: P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress. RESULTS: Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety-like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5-HT(1A) receptor partial agonist buspirone (0.6 mg/kg), and the mixed 5-HT(2C)/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal-induced anxiety-like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5-HT(2C) receptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior. CONCLUSION: These results suggest that stress-induced facilitation of alcohol drinking and withdrawal-induced anxiety-like behavior in P rats may be closely but imperfectly linked.     

Central and peripheral residual vision in humans with bilateral deprivation amblyopia

Summary Residual visual capacities were investigated in the central and peripheral visual fields of 13 patients with bilateral deprivation amblyopia secondary to congenital cataracts removed at an early age. In comparison with a control group of normal subjects, spatial modulation sensitivity function of the amblyopes was markedly impaired in each experimental condition, i.e. both when the stimuli were stationary or drifting (8 Hz) gratings and both in central or peripheral visual field, at 10 and 20° eccentricity. The sensitivity drop was observed over the whole spatial frequency range, although it was much more severe at high frequencies. Threshold elevation, with respect to controls, was very similar in conditions using stationary or drifting gratings, suggesting that both sustained and transient mechanisms are affected by stimulus deprivation amblyopia. Temporal modulation sensitivity function was uniformly impaired over the whole temporal frequency range. When compared with other types of amblyopia, this pattern of spatiotemporal sensitivity loss appeared characteristic of deprivation amblyopia. The peripheral deficit was particularly striking by its severity and extent, as ascertained by static perimetry and visual acuity measurements up to 50° eccentricity. This finding emphasizes the susceptibility of peripheral as well as central human vision to early deprivation and suggests that peripheral visual functions are still immature in newborns. Finally, the overall deficit varied with the severity of the deprivation, in that patients with complete neonatal cataract performed much worse than those with incomplete cataract.