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C Bielajew

Publications and source records attributed to C Bielajew.

At least 37 records · Page 2Linked to original sources
PubMed1996

Short-term stimulation-induced decreases in brown fat temperature.

Electrical stimulation of the ventromedial hypothalamus (VMH) has been shown to activate brown adipose tissue (BAT) thermogenesis; we hypothesized that functional links between the VMH and other hypothalamic areas may serve to regulate intrinsic VMH control of brown fat heat production. Moveable electrodes were implanted in regions surrounding the VMH in adult male rats in order to assess any acute effect of activation of these structures alone on brown fat temperature. Stimulation in the area of the ventral lateral thalamic nucleus and the zona incerta (ZI) elicited a 0.2 to 0.8 degrees C drop from brown fat baseline temperature in 48 of 55 rats; the effective sites in the ZI area are restricted to the actual band of the nucleus. Application of the alpha-adrenergic blocker phentolamine prior to restimulation of active sites yielded mixed results; these findings are compatible with a role for the vasoconstrictive action of alpha-adrenergic receptors in the regulation of BAT temperature drops. The mechanisms underlying thermoregulatory responses or diurnal temperature cycling may provide a physiological context for the findings reported here.

Adipose Tissue, Brown↗
PubMed1996

Bicuculline microinjections into the ventral tegmental area of the rat: alteration of self-stimulation thresholds and of cytochrome oxidase activity in the brain.

Abuse of drugs that potentiate GABAergic neurotransmission, namely benzodiazepines, is difficult to understand because this potentiation should elicit, among other effects, a decrease in activity within the mesolimbic system. Abuse of benzodiazepines is difficult to understand since the opposite, namely an increase in mesolimbic activity, has been implicated in drug abuse as well as in the rewarding effect of direct mesolimbic stimulation. In order to evaluate how the activity of the mesolimbic system depends on mesolimbic GABAergic influence, a GABAA receptor antagonist, bicuculline methiodide, was unilaterally injected into the ventral tegmental area and its effect on self-stimulation thresholds derived from stimulations applied to the same area was evaluated. Microinjection of 15, 20 and 30 ng increased the stimulation threshold. This decrease in stimulation efficiency lasted no more than 15 min after which baseline levels were obtained. Such a decrease is paradoxical considering that the manipulation should have released the ventral tegmentum from a tonic inhibitory influence. The metabolic consequences of repeated injections of 30 ng bicuculline were furthermore evaluated by cytochrome oxidase histochemistry. The staining was found to be weak around the injection site and dense in the ipsilateral nucleus accumbens. Release of a tonic GABAergic inhibition added to some cytotoxic damage probably resulted in an increased metabolic activity of this system. The presently reported paradoxical response of the ventral tegmentum and mesolimbic system to a GABAergic challenge may account for the paradoxical relationship between some behavioral properties of the mesolimbic system and GABAergic drugs.

Animals↗
PubMed1995

Comparison of TOBEC-derived total body fat with fat pad weights.

Total body electrical conductivity (TOBEC) predictions of overall body fat were compared to combined perirenal and epididymal fat pad weights. The latter are considered to be reasonable estimates of overall adiposity. TOBEC was used to measure the body composition of 40 male Long-Evans and two male Sprague-Dawley rats ranging in weight from 210-505 g. The animals were then sacrificed and the perirenal and epididymal fat pads were removed and weighed. Core temperature was recorded before and after TOBEC values were collected. To assess the effect of position, two values were obtained for young rats: one when the tail was tucked under the rat's body and another when the tail was extended such that the full length of the measurement chamber was occupied. The TOBEC-predicted body fat was significantly different for these two positions. The best correlation between fat pad weight and TOBEC-predicted body fat (r = 0.83) was obtained when young animals were in the tail-extended position. The reliability of TOBEC readings appears to be reasonably good with mature rats.

Adipose Tissue↗
PubMed1994

Factors that contribute to the reduced weight gain following chronic ventromedial hypothalamic stimulation.

This report follows up our earlier finding that chronic ventromedial hypothalamic stimulation caused an inhibition of weight gain. In this study we examined the contribution of stimulation-induced activity and brown adipose tissue thermogenesis to the reduced weight gain following three sessions of low-level stimulation delivered every other day to the ventromedial hypothalamus and adjacent areas. During stimulation trials, activity level was ranked on a dichotomous scale. Weight gain and food intake were subsequently monitored for an additional 4 weeks, after which the effects of a 60-s stimulation trial on the temperature of core and interscapular brown adipose tissue were evaluated. The highest activity was associated with the ventromedial hypothalamic sites and this factor contributed significantly to the difference in weight gain and food intake resulting from stimulation of the ventromedial hypothalamus and other areas. These differences largely disappeared during the follow-up period. With little exception, none of the sites elicited temperature changes in brown adipose tissue. As demonstrated in acute work, the contribution of stimulation-induced activity must be dissociated from the metabolic changes that occur in response to ventromedial hypothalamic stimulation.

Adipose Tissue, Brown↗
PubMed1994

Characteristics of stimulation-induced feeding sites in the sulcal prefrontal cortex.

Double pulse tests were used to infer the refractory periods of the substrate underlying stimulation-induced feeding in the sulcal prefrontal cortex of the rat. Eleven sites were examined, of which five supported the behaviour at currents of 250 to 400 microA; pulse duration was 100 microseconds. The average profile indicates a recovery function that begins at 0.5 ms and ends at 3.0 ms, with no apparent contribution from local potential summations. The mean effectiveness value corresponding to the asymptotic portion of the curves was 91%. These results suggest that there is substantial overlap in the excitability of neurons underlying stimulation-induced feeding in the sulcal prefrontal cortex and that reported for the medial forebrain bundle, but unlike the latter structure, there is no evidence of self-stimulation from the same sulcal prefrontal cortex placements. Response rates were collected for a maximum of 21 days from each of the cortical sites at which feeding was recorded and at the same currents used to evaluate the refractory periods underlying stimulation-induced feeding. The rates averaged between 0 and 3 responses per minute whether the current was available or not. These data represent the first demonstration of a site that supports stimulation-induced feeding in the absence of brain stimulation reward, at least at these specific placements and stimulation parameters.

Animals↗
PubMed1994

Diazepam facilitates stimulation-induced feeding in rats.

The effect of diazepam on the trade-off function between current and frequency for stimulation-induced feeding was evaluated in five rats with electrodes implanted in medial forebrain bundle structures. Three of the five exhibited stimulation-induced feeding (SIF) in vehicle tests, while in the remaining two attention to food was interspersed with periods of high activity. In all cases diazepam facilitated stimulation-induced feeding; the expression of stimulation-induced feeding was observed at a dose of 2.5 mg/kg and 5.0 mg/kg, where tested, and frequency threshold shifts ranged from 10% to 25%. The degree of facilitation was consistent across currents in two of the four pairs of trade-off functions examined. The results suggest that diazepam can facilitate stimulation-induced feeding and its expression in feeding sites with a competing arousal component.

Animals↗
PubMed1992

Behaviourally derived estimates of excitability in striatal and medial prefrontal cortical self-stimulation sites.

The refractory periods of the substrate underlying brain-stimulation reward were investigated in three rats with moveable electrodes implanted in the rostral caudate-putamen and the medial prefrontal cortex. Acquisition of caudate-putamen self-stimulation occurred within the first session, while self-stimulation for medial prefrontal cortex was observed only after three sessions of caudate-putamen stimulation. The currents required for self-stimulation ranged from 300 to 800 microA (0.1 ms pulse duration) across animals; the maximum response rates averaged roughly 40 bar presses per minute for both structures. Refractory period estimates were obtained from ten caudate-putamen and four medial prefrontal cortex sites. The time course of recovery had the following profile: the curves began to rise at 0.65 ms and 0.95 ms for caudate-putamen and medial prefrontal cortex stimulation, respectively, thereafter increasing to approach an asymptote at 6.00 ms for the caudate-putamen and 6.25 ms for the medial prefrontal cortex. The mean effectiveness value corresponding to the asymptotic portion of the curves was 73% for the caudate-putamen and 69% for the medial prefrontal cortex. Like other forebrain structures, the behaviourally derived refractory periods underlying caudate-putamen and medial prefrontal cortex stimulation, at least at these particular sites, are significantly longer than those observed in most medial forebrain bundle areas, both beginning and ending later. One interpretation for the similarity in their refractory period profiles and the apparent facilitating effect of caudate-putamen stimulation on acquisition of medial prefrontal cortex self-stimulation is that these two regions form part of the same reward substrate.

Animals↗
PubMed1991

Diazepam alters brain-stimulation reward thresholds in seizure-prone sites.

Studies of the effect of diazepam and related compounds on the rewarding properties of brain stimulation as measured by response rates have not yielded clear results, with self-stimulation performance reported to be potentiated, diminished, or unchanged following drug administration. In this study, the effect of two doses of diazepam (2.5 and 5.0 mg/kg) and its vehicle on self-stimulation thresholds was examined in eight rats with electrode placements scattered along a 4 mm length of the medial forebrain bundle. Stimulation of the lateral preoptic area and the anterior and mid-lateral hypothalamus produced overt seizures. Rate-period curves were generated for a wide range of currents and the resulting period-current trade-off functions were compared across doses. In seizure-prone sites upward shifts in period threshold were observed after 2.5 mg/kg of diazepam with little additional increases incurred by the 5.0 mg/kg dose. The majority of non-seizure sites showed no effects of diazepam upon period threshold. The results suggest that diazepam alters brain-stimulation reward thresholds by suppressing competing seizure activity.

Animals↗
PubMed1991

The effects of chronic ventromedial hypothalamic stimulation on weight gain in rats.

The effects of chronic stimulation of the ventromedial hypothalamus and adjacent structures on body weight, food intake, and epididymal fat pad weight were examined in normophagic rats. Three hours of intermittent low level electrical stimulation were delivered three times per week for four weeks; body weight and food intake were monitored for an additional ten days after stimulation trials had ceased. Animals receiving ventromedial hypothalamic stimulation had the shallowest growth curves while stimulation of other structures produced a rate of growth that fell between that of the ventromedial hypothalamic and the implanted control group. This pattern persisted during the poststimulation phase. Food intake, while initially depressed in the stimulated groups, began to approach control levels by the third week of stimulation. Efficiency of food utilization (weight gain/consumption) was significantly reduced during the first week of stimulation in the ventromedial hypothalamic stimulated group. Fat pad weight was slightly decreased in this group as well. These findings suggest that chronic stimulation of the ventromedial hypothalamus causes a persistent shift in metabolic rate that results in a long-term inhibition of weight gain.

Adipose Tissue↗
PubMed1991

Ventromedial hypothalamic regulation of brown adipose tissue.

The central control of brown fat thermogenesis was evaluated in seventeen rats with moveable electrodes implanted in the ventromedial hypothalamus (VMH) and adjacent structures. Brown adipose tissue and core body temperatures were monitored in response to VMH stimulation; sites which elicited a rise in brown fat temperature were observed in the dorsomedial and anterior ventromedial hypothalamus, with BAT temperature profiles varying widely in duration and peak values. Given the complexity of BAT responses to endogenous VMH signals, these varied profiles may be mediated by dissimilar VMH signals, which remain to be characterized.

Adipose Tissue, Brown↗
PubMed1990

Task difficulty increases thresholds of rewarding brain stimulation.

The effect of increasing task difficulty on the threshold of rewarding, electrical brain stimulation was evaluated. Rats were trained to press a lever to obtain a brief burst of pulses to the lateral hypothalamus. The threshold was psychophysically scaled using a descending method of limits in which the pulse frequency was varied to yield a maximum to minimum range of self-stimulation rates. As expected, weighting the lever with 0, 15, 30, or 45 g produced progressive decreases in maximal rates, but it also caused a weight-related shift to the right of the rate-frequency ogives in each of the 7 rats. Although the degree of shift varied from rat to rat, it did not matter whether criterion performance was defined as half-maximum rate or as a constant rate of 5 responses. These results suggest that the effort required to make the operant response contributes to the position of rate-frequency curves and, further, that shifts in rate-frequency functions must be interpreted with caution when such shifts are obtained by CNS lesions or drug injections.

Animals↗
PubMed1987

Refractoriness of neurons mediating intracranial self-stimulation in the anterior basal forebrain.

The post-stimulation excitability of neurons mediating electrical self-stimulation of the anterior basal forebrain was evaluated psychophysically in the rat. Rats with electrodes in the nucleus accumbens, caudate nucleus, lateral preoptic area, diagonal band, or anterior medial forebrain bundle pressed a lever to earn 0.5-s trains of conditioning (C) and test (T) pulse pairs. The C-T interval was systematically varied and the effectiveness of the T-pulse was estimated by measuring the frequency of pulse pairs required to sustain criterion responding. All sites tested demonstrated similar recovery; T-pulse effectiveness, normalized against the effect of the C-pulse, was lowest at delays of 0.4-0.8 ms and it rose monotonically until 5 ms when it achieved an effectiveness plateau of one. Increasing the current of the T-pulse by 50 or 60% failed to hasten recovery, suggesting that the recovery profiles primarily reflect the activation of neurons very soon after emergence from absolute refractoriness. Compared to lateral hypothalamic and ventral tegmental self-stimulation, the neurons that support self-stimulation in the ventral basal forebrain recover more slowly; recovery here is only about half done by the time lateral hypothalamic placements demonstrate complete recovery.

Animals↗
PubMed1987

The effect of pulse duration of refractory periods of neurons mediating brain-stimulation reward.

The post-stimulation excitability characteristics of neurons mediating the rewarding effects of electrical stimulation of the medial forebrain bundle were behaviorally assessed at 5 different pulse durations. Recovery from refractoriness was inferred from the results of double-pulse tests in which the interval between conditioning (C) and test (T) pulses of equal amplitude was varied. Pulses of 0.1-0.5 ms had little effect on the time course of recovery which ranged from 0.4 to about 1.5 ms in each animal. In some subjects, however, complete recovery from refractoriness was significantly delayed with 1- and 2-ms pulses, with as much as a tripling in the C-T interval at which recovery approached asymptotic levels. This effect appeared to be placement-specific and was well correlated with the threshold charge, which ranged from 0.5 to 1.3 microC. The highest charge values were obtained in those subjects in which longer pulses displaced the refractory period profile towards a slower recovery; the electrode tips in this group were located in more anterior positions than those subjects in which pulse duration had no effect on recovery from refractoriness. It appears that at some placements slowly recovering elements can contribute to the circuitry underlying brain-stimulation reward when suitable stimulation parameters are employed.

Animals↗
PubMed1986

6-Hydroxydopamine treatment enhances excitation of cultured cerebellar neurons by glutamate.

Explant cultures containing identifiable cerebellar cortical neurons and locus coeruleus neurons were treated with 500 microM 6-hydroxydopamine. At this concentration, locus coeruleus neurons were usually degenerated after 48 h, while the cerebellar cortical neurons had a normal appearance. Extracellular recording and iontophoresis of noradrenaline and glutamate were used to test for changes in electrical activity or neurotransmitter responsiveness of the cerebellar neurons. At 4-5 days following the toxin exposure, spontaneous spiking activity appeared similar to that in control cultures. Mean iontophoretic currents required to give noradrenaline-induced depressions of activity were somewhat lower for the toxin-treated cultures than for controls but not significantly so. The mean currents for glutamate excitations, however, were markedly lower in the treated cultures. Noradrenaline potentiations of glutamate responses were observed in both treated and control cultures. The greatly increased sensitivity of cerebellar neurons to glutamate does not seem related to degeneration of granule cells in the treated cultures but might be explained by disruption of astrocytic uptake mechanisms for glutamate.

Action Potentials↗
PubMed1986

Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle.

The role of ascending and descending fibers in self-stimulation of the lateral hypothalamus and ventral tegmental area in the rat was assessed by noting whether anodal hyperpolarization of one of these sites could reduce the rewarding effect of stimulating the other site. Strength-duration curves were obtained by psychophysical means, with one of the depth electrodes serving as the cathode and the other as the anode. It was anticipated that at long pulse durations, conduction in some of the fibers stimulated at the cathode would be blocked at the anode. At shorter durations, the anodal hyperpolarization should have dissipated before the arrival of the action potentials triggered by the cathode. Thus, the predicted effect of the block was to bend the strength-duration curves obtained with two depth electrodes upward at long pulse durations, provided that the anode lay between the cathode and the efferent stages of the pathway responsible for the rewarding effect. To control for possible differences in the density of the reward substrate in the lateral hypothalamic and ventral tegmental areas, the strength-duration curves obtained with a given cathode and a depth anode were compared to curves obtained with the same cathode but with an anode consisting of a set of skull screws. It was expected that the concentrated current entering from the depth anode would much more effectively block conduction in the medial forebrain bundle than the diffuse current entering from the large, distant skull screws. The predicted change in the shape of the strength-duration curves was observed only when the ventral tegmental electrode served as the anode and the lateral hypothalamic electrode as the cathode. This is consistent with the notion that in at least some of the neurons responsible for the rewarding effect, action potentials elicited by the lateral hypothalamic electrode had to pass through the ventral tegmental area in order to reach the efferent stages of the reward pathway. In the simplest anatomical arrangement consonant with this view, the somata of these cells lie in the forebrain and give rise to descending axons. As a test of the hypothesis that anodal block was responsible for changing the shape of the strength-duration curve obtained with the ventral tegmental anode, a psychophysical version of the collision test was used to determine whether the tips of the lateral hypothalamic and ventral tegmental electrodes were indeed linked by a common set of reward-related fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Behaviorally derived measures of conduction velocity in the substrate for rewarding medial forebrain bundle stimulation.

The results of collision and refractory period tests were used to compute conduction velocity estimates for reward-relevant neurons activated by electrodes aimed approximately 3 mm apart along the trajectory of the medial forebrain bundle (MFB). Collision tests consisted of delivering pairs of pulses in alternating fashion to the lateral hypothalamus and ventral tegmental area. As the interval between pulses was increased the behavioral effectiveness of double-pulse stimulation abruptly increased and then levelled off at longer pulse-pair intervals. In 6 subjects the C-T interval at which the abrupt rise was observed ranged from 1.0 to 3.0 ms. Refractory periods were estimated using an analogous paradigm but with both pulses applied through the same electrode. Recovery was first evident at pulse-pair intervals greater than 0.4-0.6 ms. Conduction velocity was determined for each subject by dividing the interelectrode distance by the difference between the collision interval and the refractory period; a range of 1.0-4.5 m/s was obtained, values that are inconsistent with the reported conduction velocities for catecholaminergic fibers. It is proposed that the substrate for brain-stimulation reward in the MFB consists of small, myelinated, non-catecholaminergic fibers.

Animals↗
PubMed1982

Absolute and relative refractory periods of the substrates for lateral hypothalamic and ventral midbrain self-stimulation.

The pulse-pair paradigm was used to behaviorally assess the absolute and relative refractory periods of neurons subserving brain-stimulation reward. The amplitude of the second pulse was either equal to, 41% greater than, or 73% greater than the amplitude of the first pulse. In the equal amplitude condition, recovery from refractoriness began as early as 0.4 msec and did not asymptote until as late as 3.5 msec. A 41% increase in the intensity shortened the time course of recovery in five out of six cases. In only one of these five cases did a 73% increase in the intensity of the second pulse produce further changes in time course. Neither increase in the amplitude of the second pulse affected the time course of recovery in one subject. The absolute refractory periods of the directly stimulated reward-relevant neurons appear to be less than 1.5 msec and as short as 0.4 msec; some of these neurons have relative refractory periods that range between 1.0 and 3.5 msec.

Animals↗