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Biomedical subjects

G Fouriezos

Publications and source records attributed to G Fouriezos.

At least 19 recordsLinked to original sources
PubMed2004

Short- and long-term effects of interleukin-2 on weight, food intake, and hedonic mechanisms in the rat.

In the present work, we investigated the short- and long-term effects of a single systemic injection of rat recombinant interleukin-2 on weight, food intake, and brain stimulation reward thresholds elicited from the ventral tegmental area. An inverted U-shaped dose-function was obtained with 0.5 microg producing the greatest increases in the threshold for rewarding brain stimulation which were sustained during the month long tests. No differences between groups in terms of maximum response rates, a measure of performance, were observed. Although all injected groups showed a minor decline in the rate of weight gain over time, percent efficiency of food utilization (percent weight gain/food intake) was the same across groups, suggesting that metabolic function was not affected by the cytokine. In animals with bilateral ventral tegmental area implants, there was no consistent correspondence between the threshold change obtained from ipsilateral stimulation and that associated with the contralateral site; side-to-side differences ranged from 0 to 100%, suggesting a specific interaction between cytokine activity and the locus of rewarding brain stimulation. These data suggest that peripheral IL-2 significantly modifies hedonic processes arising from medial forebrain bundle stimulation in a long-term manner. We further suggest that since this modulation appears to be notably site-specific, IL-2 receptors or its metabolites may not be evenly distributed within the medial forebrain bundle.

Animals↗
PubMed2003

Strain and gender specific effects in the forced swim test: effects of previous stress exposure.

The chronic mild stress (CMS) procedure was developed in rodents to target anhedonia, the core symptom of depressive melancholia. Stress exposure has been shown to induce a variety of physiological, biochemical and behavioral alterations associated with depression, although its anhedonic consequences as indexed by either sucrose intake and preference or thresholds for brain stimulation reward are less reliably observed. In the present study, we assessed the effects of six weeks of CMS on the latter measure in two strains of male and female rats subsequently challenged with an acute psychophysical stressor, forced swimming; their behavior in the swimming cylinder was evaluated on two consecutive days. While brain stimulation reward thresholds and response rates were unchanged by CMS exposure, significant differences in forced swim behaviors were observed between male control and CMS groups. In particular, male Long Evans rats with a history of CMS showed the largest decrease in the duration of active behaviors on the second test day, a pattern less evident in the Sprague-Dawley strain of rats, or in any of the female groups. The results suggest that the effects of depressogenic manipulations are strain and gender dependent, with male Long Evans rats most susceptible, as demonstrated by the selective reduction of struggling behaviors. Inclusion of multiple measures, including the forced swim test, would provide a better understanding of the psychopathological profile engendered by chronic exposure to mild stressors and its genetic specificity.

Animals↗
PubMed2001

The substrate for brain-stimulation reward in the lateral preoptic area: III. Connections to the lateral hypothalamic area.

Double-pulse tests were used to estimate the refractory periods and anatomical linkage of the reward-relevant fibers that course between the lateral preoptic and lateral hypothalamic areas. In the 1st study, pairs of conditioning and test pulses were delivered to each site, and the interval between pulses varied; recovery from refractoriness was similar at both sites, with the curves generally rising from 0.6 to 2.0 ms. In the 2nd study, the pairs of pulses were delivered to both sites. Six of 7 rats showed evidence of axonal collision, with estimates of conduction velocity that ranged from 0.48 to 8.95 m/s across rats. These results suggest that a wide spectrum of fiber types characterizes the reward-relevant axons that course uninterruptedly between these 2 regions.

Action Potentials↗
PubMed2001

Measuring threshold shifts for brain stimulation reward using the method of limits.

Thresholds determined from the frequency of pulses and the current for rewarding brain stimulation were obtained from rats with lateral hypothalamic electrodes. The threshold, defined as the frequency or current corresponding to one-half the maximum response rate, was interpolated from reward summation functions. Daily trials of both ascending and descending sequences of frequency and current yielded no significant difference between order of presentation. While there was more variability in the maximum response rates across the sessions, neither frequency- nor current-based threshold evaluations yielded significant rate effects. Our findings suggest that the threshold procedure is generally not influenced by the sequence of delivery of stimulus values and, thus, may be regarded as a reliable measure of the reinforcing properties of brain-stimulation reward.

Analysis of Variance↗
PubMed1997

The cost of delaying rewarding brain stimulation.

Six rats trained to press a lever to obtain rewarding electrical stimulation of the brain through chronically implanted, lateral hypothalamic electrodes were used to estimate the rate at which short delays between the response and the reward degraded the rewarding effect of the stimulation. Frequency thresholds rose steadily with delays through to 2.2 s at a rate of 10% per second.

Animals↗
PubMed1996

Intermittent rewards raise self-stimulation thresholds.

Rats implanted with lateral hypothalamic electrodes pressed a lever to obtain 0.5 s bursts of pulses under the four combinations of fixed or variable, interval or ratio, schedules of reinforcement. Along with continuous reinforcement schedules, intervals of 1, 2, 5, and 10 s, or ratios of 2, 5, and 10 responses per stimulation were used in sessions wherein the frequency thresholds, defined as pulse frequencies that would support half-maximum rates of response, were estimated. Thresholds rose systematically under both ratio and interval schedules of reinforcement, and there was no difference between fixed and variable variations. When normalized data were plotted as a function of reinforcement density, thresholds from both interval and ratio schedules followed the same pattern, suggesting that the common factor was time between rewards. An increase in the current with a corresponding decrease in pulse frequency increased the rate at which time between rewards augmented thresholds.

Animals↗
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

Integration of free pulses in electrical self-stimulation of the rat brain.

Frequency thresholds for electrical self-stimulation of the medial forebrain bundle were estimated in rats while low frequencies of pulses were applied continuously. When continuous pulses were delivered to the same electrode that received the 0.5-s trains of response-initiated stimulation, thresholds decreased by the free-pulse frequency (Experiment 1), consistently across current (Experiment 2). Estimates of the reward added by concurrent, response-contingent stimulation of the opposite electrode of a bilateral pair predicted the drop in threshold caused by the noncontingent pulses applied to the opposite hemisphere (Experiment 3), again, robustly across test current (Experiment 4). Continuous pulses restricted to times between self-initiated trains lost their effect (Experiment 5). The perception of reward was invariant despite changes in the overall activity of the self-stimulation substrate.

Animals↗
PubMed1995

Temporal integration in self-stimulation: a paradox lost?

Seven self-stimulating rats with electrodes located along the medial forebrain bundle were used to study how excitation dissipates at the end of a train of rewarding electrical pulses. On a 5-s, fixed-interval schedule, the rats pressed a lever to obtain 2 trains of pulses separated by gaps of up to 2 s; the first train was fixed at a just-subthreshold number of pulses, whereas the second train was used to scale the number of pulses needed to just support consistent responding. The number of pulses needed grew with increasing gaps between the 2 trains, rapidly at first and then decelerating to an asymptote, with time constants of a few tenths of a second. These results support C. R. Gallistel's (1974, 1978) model of leaky integration of rewarding brain stimulation.

Animals↗
PubMed1992

Apomorphine and electrical self-stimulation of rat brain.

The participation of dopamine neurons in reward produced by electrical stimulation of the brain was examined by measuring self-stimulation thresholds after injections of apomorphine, a direct agonist of dopamine receptors. Rats were trained to press a lever to obtain 0.3-s trains of electrical stimulation applied to lateral hypothalamic electrodes in a paradigm where the pulse frequency was decreased every eight stimulations by approximately 20%. The pulse frequency interpolated at 50% of maximum rate was taken as threshold. In a completely within-subject design, five doses of apomorphine from 0.01 to 1.00 mg/kg and the ascorbic acid vehicle were injected in a random order and thresholds were tracked at intervals of 5 min for 2 h postinjection. Low doses from 0.01 to 0.10 mg/kg caused thresholds to increase while the two higher doses, 0.30 and 1.00 mg/kg, caused thresholds to drop; the switch in the direction of the behavioural effect is thought to parallel the shift in apomorphine's action from presynaptic to predominantly postsynaptic activation of dopamine receptors as the concentration of apomorphine increases.

Animals↗
PubMed1992

Pulse jitter retards kindling without affecting brain-stimulation reward.

Convulsions in rats bar-pressing for electrical stimulation of the brain can interfere with the behavioural evaluation of the properties of the reward substrate. If seizure activity involves the synchronous activation of populations of neurons, then the regular timing of pulses may be important in epileptogenesis produced by electrical stimulation. In the first experiment we found that behaviourally derived, charge-duration functions collected from three self-stimulating rats with lateral hypothalamic electrodes were not affected by introducing a controlled, 50% jitter to the interpulse interval of self-stimulation trains. In the second experiment, we kindled two groups of 6 rats with once-daily, 1.0 s bursts of either regularly timed or jittered pulses to the amygdala until full motor seizures developed. Although both groups eventually attained Class 5 convulsions, the time to first seizure was about two days longer with jittered pulses. Thus, while the circuitry that accumulates input from self-stimulation is not affected by the irregularity of asynchronous pulses, the jitter does seem to retard the development of seizures.

Amygdala↗
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↗
PubMed1984

Current-distance relation for rewarding brain stimulation.

A novel approach to estimating the current density required to directly activate axons involved in the reinforcing effect of brain stimulation is described. Self-stimulating rats received trains of cathodal pulse pairs via two adjacent, stimulating electrodes which were positioned in the lateral hypothalamus and oriented to lie in a plane transverse to the medial forebrain bundle. The first pulse of each pair was delivered through one electrode and, after varied delays, the second was applied to the other electrode in an attempt to detect a loss of stimulation effectiveness attributable to refractoriness of axons that penetrated the intersection of the two stimulation fields. In low-current tests, no change in the psychophysically scaled effectiveness was observed as the interval separating the pulses was varied but, at higher currents, the stimulation effectiveness rose when the delay between the pulses surpassed the refractory periods of these cells. Our inference was that greater currents produced progressively overlapping stimulation fields. Moreover, evidence of overlap was seen at lower currents in rats that had been prepared with smaller separations between the electrodes. Our estimate of the threshold current density for the most sensitive of the reward units is 1300 microA/mm2 when 0.1 ms pulses are used.

Animals↗
PubMed1980

Influence of substance P on the behavioral changes induced by haloperidol in rats.

Locomotor activity and grooming behavior of rats were recorded for a period of 30 min following intraventricular injections of substance P(SP) in doses of 0.60 and 2.50 microgram/rat. The lower dose of the peptide significantly increased locomotion for 10 min and time spent grooming for 25 min. The effects of the same two doses of SP on the hypokinesia induced by various pharmacological treatments modifying catecholaminergic systems were then examined. SP did not affect the behavioral depression produced by alpha-methyl-para-tyrosine (250 mg/kg), FLA-63 (25 mg/kg) and phenoxybenzamine (20 mg/kg). However, SP, in dose of 0.60 microgram/rat, systematically reversed the decrease in locomotor activity induced by a relatively small dose of haloperidol, 0.1 mg/kg. The dame dose of the peptide significantly counteracted the rigidity but not the hypokinesia and catalepsy resulting from the previous administration of a higher dose of haloperidol, 3 mg/kg. The results support the hypothesis that SP may exert direct or indirect function in motor behavior, possible via a modulatory action on brain dopaminergic systems.

Animals↗
PubMed1978

Neuroleptic-induced attenuation of brain stimulation reward in rats.

In 30-min free-operant tests, the dopamine receptor blockers pimozide (.125, .25, and .50 mg/kg) and (+)-butaclamol (.1, .2, and .4 mg/kg) attenuated lever pressing for lateral hypothalamic brain stimulation. When discrete self-stimulation trials were offered in a straight alleyway, pimozide increased start box latencies, slowed running speeds, and reduced lever-pressing rates. However, performance early in both lever-pressing and runway sessions was normal; performance deteriorated as testing progressed, following patterns that paralleled those seen when animals were tested with reductions in the amplitude of stimulating current. Spontaneous recovery was obtained in both situations; experimenter-imposed 10-min time-outs caused renewed lever pressing and running. In contrast, alpha-noradrenergic receptor blockade by phenoxybenzamine (5, 10, and 20 mg/kg) failed to produce extinction-like response patterns. These data support the view that central dopaminergic systems are important components of the neural mechanisms mediating reward.

Animals↗