Line defects in gel phase lipid monolayers.

We investigate various models of the hydrolysis of gel-phase phosphatidylcholine monolayers by phospholipase A2 (Grainger et al. (1989) FEBS Lett. 252, 73-82). We assume that the probability of hydrolysis of a given lipid depends only upon how many of its nearest neighbour lipids have already been hydrolysed. We find that the experimental data are consistent with a model in which line defects exist in the gel phase and that lipids on such defects are more easily hydrolysed than the other gel-phase lipids. Based on this model, we calculate the course of hydrolysis of a gel-phase region possessing line defects, and we suggest how such a structure might be made and the model tested. An experiment, similar to that proposed by us, has been carried out by Grainger et al. (1990) Biochim. Biophys. Acta 1023, 365-379). We also calculate the fractal dimension, df, of the interface created by the hydrolytic process and show that a measurement of df might identify how this process proceeds.

Behavioral characterization of intracranial self-stimulation from mesolimbic, mesocortical, nigrostriatal, hypothalamic and extra-hypothalamic sites in the non-inbred CD-1 mouse strain.

A behavioral analysis of intracranial self-stimulation (ICSS) was provided for mesolimbic/mesocortical, nigrostriatal, hypothalamic and extrahypothalamic sites in the CD-1 mouse. Robust responding and rapid acquisition of mesocortical ICSS appeared dorsally along notably fluorescent sites in rostral and caudal planes. ICSS was diminished demonstrably in medial and ventral positions in posterior planes. Mesolimbic ICSS from the medial and ventral nucleus accumbens (Nas), was accompanied by significant elevations in locomotor activity, corresponding to regions of dopamine (DA) and cholecystokinin co-localization. Stimulation-induced seizures appeared from both the Nas as well as the mesocortex. ICSS from the ventral tegmental field (VTA) was evident along its medial, lateral and dorsal borders with longer pulse durations more likely to elicit responding. Seizure activity was absent from the VTA. Striatal ICSS was conspicuously poor in dorsal and medial locations; regions presumably devoid of tegmental innervation. ICSS emerged from both the ventrocaudal and anteromedial striatum; regions linked to innervation by the dorsolateral and ventromedial VTA. The red nucleus, a previously neglected self-stimulation site supported marked responding for ICSS. Regions supporting rubral ICSS were correlated with thalamic innervation sites; notably the ventrolateral thalamic nucleus and the parafascicular nucleus, regions found to support ICSS. The substantia nigra supported high rates of responding for ICSS when electrode placement was restricted to the dorsomedial portion of the pars compacta. Electrode deviations lateral and dorsal to the substantia nigra pars medialis induced a progressive decline in responding. Hypothalamic sites were found to support significant responding for ICSS, although such performance was frequently associated with seizure induction. Taken together these data (1) provide the first behavioral analysis of ICSS in mice responding from previously unexamined DA sites in the mesolimbic (e.g. VTA, Nas) and nigrostriatal systems (e.g. caudate, red nucleus) (2) suggest an anatomical reconsideration of the assumptions underlying the elicitation of ICSS from the frontal cortex (3) suggest that the neural circuitry underlying thalamic, caudate, rubral and frontal cortical ICSS are interrelated and (4) suggest that the Nas and the frontal cortex, like the hypothalamus, in the mouse appear to be particularly sensitive to stimulation-induced seizures.

Stressor induced variations of intracranial self-stimulation from the mesocortex in several strains of mice.

Intracranial self-stimulation (ICSS) from the mesocortex was assessed in BALB/cByJ, C57BL/6J and DBA/2J mice immediately, 24 h and again 168 h following stressor application. Stressor exposure failed to influence ICSS performance in C57BL/6J mice, while self-stimulation performance was reduced among BALB/cByJ mice only in the immediate post-stressor interval. In contrast, DBA/2J mice exhibited reduced rates of responding for brain stimulation at each of the post-stressor intervals. The potential contribution of DA alterations to the strain-dependent variations of ICSS performance induced by uncontrollable footshock are discussed.

Stressor-induced behavioral alterations in intracranial self-stimulation from the ventral tegmental area: evidence for regional variations.

Exposure to uncontrollable footshock reduced responding for electrical brain stimulation (ICSS) from the ventral tegmental area (VTA) of the CD-1 mouse. Such an effect, however, varied with electrode position in the tegmental field. In both a rate-dependent and a current intensity paradigm, ICSS from the dorsal VTA was reduced immediately, 24 hr and 168 hr following exposure to acute uncontrollable footshock. In contrast, ICSS from the ventral VTA was unaffected by the stressor regimen. These data are consistent with the suggestion that a stressor may reduce the rewarding value ordinarily derived from ICSS. Inasmuch as the stressor differentially affected ICSS from the dorsal and ventral tegmentum, these data provide evidence for a functional differentiation within the midbrain tegmental area.

Proactive influence of a surgical stressor on locomotor activity, exploration and anxiety-related behaviour following acute footshock in the mouse.

The putative proactive influence of graded surgical stressors including intraventricular cannulation, sham surgery and no surgery on footshock-associated variations of locomotor activity, rearing and anxiogenic behaviour in the light-dark paradigm was evaluated among CD-1 mice. Neither sham surgery nor cannulation of the lateral ventricle altered baseline measures of locomotor activity or rearing relative to the performance of nonoperated control animals. Cannulation exacerbated the depressant influence of acute footshock on locomotor activity, while sham surgery mitigated the disruptive effect of the stressor on locomotor activity during the initial 15-min period of the test session. Footshock suppressed the vertical activity scores of mice regardless of surgical history. Only intraventricular cannulation reduced the baseline time in light scores of mice in the light-dark paradigm with repeated testing relative to animals in the sham surgery and no-surgery conditions. Baseline transition scores were not differentially affected by surgical history. Typically, transition scores were reduced on day 2 relative to day 1, but additional performance decrements were precluded on day 3. Footshock interacted with the surgical stressor of intraventricular cannulation in exaggerating reduced time in light relative to the performance of mice in the remaining surgical conditions. Transition frequency was not differentially influenced by the nature of the surgical stressor and subsequent exposure to footshock. The implications of these data for stressor-induced pathology are discussed.

Aluminum retention by aged rats fed aluminum and treated with desferrioxamine.

Our primary purpose was to assess the impact of chronic exposure to dietary aluminum on aging rats. Male rats were fed diets containing 0.4 or 36.8 mumol Al/g diet for 8 months until 23 months of age. The aging rats fed supplemental aluminum accumulated more aluminum in sera, tibias, and kidneys than control rats, but accumulated similar concentrations of aluminum in bone as young rats fed aluminum for short periods of time in previous studies. Although the rats had increased bone turnover (as indicated by urinary hydroxyproline excretion) after 22 months of age, the amount of bone turnover was not sufficient to explain the urinary excretion of aluminum by the aged rats.

Anxiogenic behavior in the light-dark paradigm follwoing intraventricular administration of cholecystokinin-8S, restraint stress, or uncontrollable footshock in the CD-1 mouse.

The influence of restraint stress (0, 15, 30, or 60 min), uncontrollable footshock (0, 15, 30, or 60 shocks), or intraventricular CCK-8S administration (0, 5, 25, or 50 ng delivered in a 1 microliter volume) were evaluated on transition frequency and cumulative time in light among CD-1 mice in the light-dark paradigm. Mice exposed to restraint stress of either 15 or 60 min were indistinguishable from nonrestrained animals, while the 30-min session of restraint decreased time in light and transition scores. The presentation of 15, 30, or 60 uncontrollable footshocks were equally effective in decreasing cumulative time in light but had no effect on transition scores. Intraventricular infusion of 25 and 50 ng doses of cholecystokinin-8S reduced cumulative time in light and transition frequency in CD-1 mice relative to vehicle or 5 ng CCK-8S-treated animals in the light-dark paradigm. The time in light and transition data secured among mice with repeated light-dark exposure and 30 min of restraint were comparable to the corresponding scores secured when performance was only evaluated on trial 1. Transition scores were reduced on trial 1 of mice exposed to 30 min of footshock, but time in light was reminiscent of the performance detected among mice with prior light-dark experience. Potential neurochemical correlates associated with the anxiogenic effects associated with stressor exposure and CCK-8S administration in the light-dark task are discussed.

Differential effects of immunologic challenge on self-stimulation from the nucleus accumbens and the substantia nigra.

Paralleling the effects of uncontrollable stressors, systemic administration of sheep red blood cells (SRBC) provokes brain neurotransmitter alterations, including DA variations within mesocorticolimbic regions, coinciding with or slightly preceding the peak immune response. Inasmuch as stressors disrupt responding for brain stimulation from the nucleus accumbens, possibly reflecting the anhedonic consequences of stressors, the present investigation assessed whether antigenic challenge would also influence responding for brain stimulation. Sheep red blood cell administration was found to reduce responding for brain stimulation from the nucleus accumbens, without affecting performance from the substantia nigra. The alterations of self-stimulation from the nucleus accumbens occurred at times that approximated the peak immune response. These data suggest that antigenic challenge may induce anhedonic-like effects that may be secondary to central neurochemical alterations engendered by the treatment. The possibility is also entertained that antigenic challenge may be interpreted as a stressor and contribute to alterations of affect.

Tissue turnover of aluminum and Ga-67: effect of iron status.

The purposes of this study were to evaluate the effect of nutritional status in regard to iron on aluminum distribution and turnover and to evaluate Ga-67 as a marker for aluminum. Anemic (n = 27) and normal (n = 30) rats were dosed by gavage with 0.8 mmoles of aluminum and 20 microCi Ga-67 in a 0.75 mol/l citrate solution and sacrificed 1, 3, 6, 9, 15, and 21 days later. Anemic rats generally retained more aluminum in their livers but less in tibias and spleens than normal rats. The half-lives of aluminum in liver (56 vs 17 days), muscle (33 vs 16 days), and serum (12 vs 8 days) were significantly greater in anemic than normal rats, respectively. Total body retention of Ga-67 could be described on the basis of a two-compartment model. The turnover of Ga-67 from the first compartment was rapid (half-life = 0.8 and 0.6 days) in anemic and normal rats, respectively, and was similar to the turnover of Ga-67 from the Gl tract (half-life = 0.7 and 0.6 days in anemic and normal rats, respectively). The turnover of Ga-67 from the second compartment was also rapid (2.8 vs 4.0 days in anemic and normal rats, respectively). Anemia affected the retention of Ga-67 more than the retention of aluminum; anemic rats retained more Ga-67 in their livers, spleens, kidneys, hearts, and muscles but less in their tibias than normal rats. In general, Ga-67 was not a satisfactory marker for aluminum distribution and turnover in normal and anemic rats.

Psychosocial moderators of substance use among middle school-aged adolescents.

Recent statistics show a decrease in the overall use of drugs and alcohol in the general population [1]. In sharp contrast to this trend is the indication that adolescents' use of drugs and alcohol is increasing [2]. Because the use of drugs and alcohol can have serious implications for adolescents' physical, emotional, and social development, it is important that human service practitioners working with them understand those factors that influence their substance use, in order to develop effective interventions to deal with this growing problem. This article reports the findings of a study of drug and alcohol use among a sample of 779 adolescents who attended middle schools in a large urban city in the southwest United States. The study examines the relationships between substance use, social support, and a variety of other psychosocial factors. The implications of those relationships for human service practice and research are discussed.