Biomedical subjects

E Miliaressis

Publications and source records attributed to E Miliaressis.

At least 19 recordsLinked to original sources

PubMed2001

Factors that influence the persistence of stimulation-induced aversion.

Brain stimulation reward in certain regions has been shown to produce analgesia to externally applied painful stimuli. In the present experiments, we studied how electrical self-stimulation of the dorsal raphe (DR) nucleus modifies the aversive effects of electrical stimulation of the nucleus reticularis gigantocellularis (Gi) or of the dorsal tegmentum (DTg). In the first study, the threshold for latency to escape aversive Gi stimulation was tracked before and after exposure to rewarding DR stimulation. Only a few sessions of DR self-stimulation were required to produce a complete and long-lasting inhibition of Gi aversion. In the second study, the aversion induced by DTg stimulation rapidly disappeared following a few test sessions at that site. Unlike our previous experience with Gi aversion that required either pairing with rewarding lateral hypothalamic (LH) or ventral tegmental area (VTA) pulses in order to increase the threshold for latency to escape Gi aversion, in this study, simply brief experience with rewarding DR stimulation in unpaired trials was sufficient to entirely suppress Gi-induced aversion. Even more surprising was the finding that unlike the Gi, aversion obtained from activation of the DTg does not persist, its threshold for escape quickly increases, and within a few sessions is no longer evident. One interpretation of these findings is that the aversion mechanisms associated with the Gi and DTg are differentially susceptible to analgesic processes.

Animals↗

PubMed2000

Interactions between rewarding lateral hypothalamic and aversive nucleus reticularis gigantocellularis stimulation.

The interaction between rewarding and aversive consequences of brain stimulation were assessed in two studies. In the first, the frequency threshold for 300 ms trains of combined lateral hypothalamic (LH) and nucleus reticularis gigantocellularis (Gi) stimulation, in which each LH pulse was followed 2 ms later by the Gi one, was determined for one month. Compared to the threshold for trains of single LH pulses, combined LH-Gi stimulation initially increased the frequency threshold; however, this effect reversed within one session and was subsequently maintained for the duration of the study. The aversion produced by Gi stimulation, as measured by latency to escape, was abolished following a single session of LH-Gi pairs. In the second study, a subset of animals received both presentations of combined pulses, LH followed by Gi, and the reverse; the interval between pulses was varied from 0.2 to 6.4 ms. The effectiveness of combined stimulation, determined by the ratio of LH frequency thresholds to that of the LH-Gi ranged from 0 to 50% across animals but the individual effectiveness functions within animals did not vary with different intervals. In addition, the order of presentation of pulses was of no consequence. Thus, not only did exposure to LH stimulation appear to obliterate Gi aversion, but the combination of LH and Gi pulses added to the rewarding effect produced by LH stimulation alone.

Animals↗

PubMed1997

Ventral pallidum self-stimulation induces stimulus dependent increase in c-fos expression in reward-related brain regions.

Neuronal expression of Fos, the protein product of the immediate early gene c-fos has been used as a high resolution metabolic marker for mapping polysynaptic pathways in the brain. We used Fos immunohistochemistry to reveal neuronal activation following self-stimulation of the ventral pallidum. Four groups of rats were allowed to self-stimulate for 30 min with 0.4 s trains of cathodal rectangular pulses of constant intensity (0.4 mA) and duration (0.1 ms). Each group was assigned a different pulse frequency, (3, 17, 24 and 50 pulses/stimulation train). Which was preselected from within each animal's rate-frequency function. The subjects that were assigned three pulses failed to self-stimulate and were considered as controls. The subjects that were assigned 17 pulses self-stimulated at half-maximal rate, whereas those that were assigned 24 and 50 pulses self-stimulated at maximal rates. The animals were sacrificed 90 min after the self-stimulation session and their brains were processed for Fos-like immunoreactivity. Fos-like immunoreactivity was found to increase as a function of pulse frequency in several brain regions known to be involved in drug and/or brain stimulation reward (medial prefrontal cortex, lateral septum, nucleus accumbens; lateral hypothalamus and ventral tegmental area), whereas it was not affected in structures devoid of such involvement (substantia nigra reticulata and dorsolateral striatum). The level of Fos expression induced by trains of 50 pulses was considerably higher than that produced by 24 pulses although both frequencies supported the same (maximal) self-stimulation rate. This finding indicates that Fos expression correlated with reward magnitude (known to increase between these frequencies), not with bar-pressing rate, thus suggesting the presence of a reward-specific effect. The finding of a frequency-dependent Fos expression in a behavioural paradigm can be considered analogous to a pharmacological dose-response curve and, as such, our results may open new avenues for the use of Fos immunohistochemistry in quantitative neurobehavioural studies.

Animals↗

PubMed1995

The bidirectional interaction between ventral tegmental rewarding and hindbrain aversive stimulation effects in the rat.

We used the curve-shift procedure in self-stimulating rats to examine the interaction of aversive and rewarding electrical stimuli in terms of duration and direction. The subjects were implanted with two moveable electrodes, one in a region supporting self-stimulation (the ventral tegmental area, VTA) and another in a region supporting escape (the nucleus reticularis gigantocellularis, Gi). The function relating self-stimulation rate to pulse frequency (RF function) was first obtained and then replicated in a condition where each VTA pulse was followed 0.2 or 2.0 ms later by a Gi pulse. The intensity of Gi pulses was set at a value previously found to elicit escape within less than 5 sec. The following observations were made: (1) rats self-stimulated consistently, despite the presence of Gi pulses, (2) the presence of Gi pulses shifted the RF function rightward (decreased the rewarding efficacy of VTA stimulation), with little effect on the maximum rate, (3) after 2 to 5 VTA-Gi self-stimulation sessions, the Gi pulses progressively lost their ability to shift the RF function, and (4) at the end of testing, escape was no longer detectable using Gi pulses alone. It was concluded that (1) the interaction between rewarding VTA and aversive Gi stimulation effects is bidirectional, thus suggesting the presence of algebraic summation; (2) the effect of Gi on VTA reward is transient whereas that of VTA on Gi aversion cumulates and eventually results in total abolition of Gi aversion. The present study represents the first account of cumulative and long-lasting suppression of aversion following brain stimulation in the rat.

Animals↗

PubMed1995

Ventral pallidum self-stimulation: a moveable electrode mapping study.

The distribution of electrical self-stimulation (ESS) foci within the ventral pallidum (VP) was mapped using moveable electrodes in rats. The function relating ESS bar-pressing rate to the frequency of cathodal rectangular pulses (0.4 mA and 0.1 ms) was obtained for several positions of a moveable electrode in the VP and in the various adjacent to VP nuclei. The rate-frequency functions were fitted to a sigmoid model to obtain the asymptotic rate and threshold frequency. ESS was found in almost all (98%) VP sites tested and to a lesser degree (66%) in the surrounding areas (namely globus pallidus and caudate). Depending on the VP site, maximum rates varied from 14 to 85 bar presses/min, whereas threshold frequencies varied from 10.2 to 36.4 pulses/train; no correlation between these two aspects of ESS was found. Extra-pallidal areas contained less low-frequency threshold sites compared to VP. The lowest threshold found in the VP was slightly higher than that usually obtained for the most rewarding brain areas (VTA, dorsal raphé, LH, amygdala), which suggests that the VP represents an important structure for reward. Furthermore the threshold frequencies were found to decline along the rostrocaudal axis of the VP which supports the view that the VP is heterogeneous in regard to reward related functions.

Amygdala↗

PubMed1995

Interhemispheric links in brain stimulation reward.

The MFB substrate of self-stimulation (SS) has generally been viewed as a unilateral system. We re-examined this belief with pairs of moveable SS electrodes placed bilaterally in the MFB. Rats barpressed for trains of single or twin cathodal pulses of fixed intensity and width and of variable frequency. The first (C) and second (T) pulse of each pair was delivered through the left and right electrode or inversely. C-T intervals ranging from 0.2 to 5.0 ms were tested. The frequency of C pulses required for criterial bar-pressing was used to plot the stimulation efficacy (SE), as a function of the C-T interval and pulse presentation order. The electrodes were subsequently moved and the same procedure repeated for more ventral sites. With some pairs of contralateral hypothalamic (H) sites, the SE was independent of the C-T interval. However, with other pairs of contralateral H sites, the SE increased with C-T interval in a manner resembling a collision effect, with the important exception that no conduction time (CT) was apparent in the data. The absence of CT excludes the presence of a genuine collision effect. When one pulse was sent to the H and another to the contralateral ventral tegmentum (VT), the H-VT curve rose always earlier than the VT-H curve, thus resembling a transynaptic collision effect. However, the C-T interval at which the VT-H curve began rising (always 1.0 ms or less) fails to support the contention that the electrodes activated fibers separated by a synapse. Finally, a typical collision effect was noted with ipsilateral H-VT electrode placements, confirming the presence of direct linkage between ipsilateral MFB sites. Computer-generated data based on two parsimonious assumptions were found to match the empirical results. These assumptions were that each electrode activated a different branch of the same reward neuron and that conduction failure occurred at the branchpoint. The model, which posits that a large number of MFB reward neurons send branches to the other hemisphere, is testable and makes clear-cut predictions about the effects of lesions. In a preliminary test, we recorded the H and contralateral VT threshold frequencies before and after lesioning the H. The H threshold increased more when using small pulse current and remained constant throughout the 4-week testing period. The VT threshold was elevated more for intermediate pulse current and kept increasing with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Poststimulation excitability of ventral pallidum self-stimulation neurons.

The degree of neural recovery from refractoriness was inferred in rats self-stimulating with pairs of pulses in the ventral pallidum. The prerecovery intrapair interval varied from 0.5 to 1.0 ms, depending on brain site. At some sites, recovery reached its maximum within less than 1.6 ms whereas, at the majority of sites, a substantial amount of recovery occurred at delays longer than 1.2 ms. The shortest recovery estimates were not fundamentally different from those obtained from sites lying along the medial forebrain bundle. The longest recovery estimates were similar to those obtained from cortical and basal forebrain sites. The differences in recovery noted between sites and the presence of step-like patterns in the recovery curves suggest the presence of neural heterogeneity within the ventral pallidal substrates of reward.

Animals↗

PubMed1994

Post-stimulation excitability of diencephalic self-stimulation neurons.

We used the double-pulse technique with moveable electrodes to estimate the refractory periods of self-stimulation neurons within the rat's dorsal diencephalon and surrounding areas. Refractory period estimates varied substantially depending on the site of stimulation. For some sites, recovery from refractoriness was noted at post-stimulation intervals as short as 0.5 ms, an estimate similar to that reported for the MFB axis and the dorsal raphe and periaqueductal grey. The longest recovery intervals were similar to those reported for the prefrontal cortex, caudate, and substantia nigra. Step-like recovery (believed to indicate the presence of neural populations with non overlapping refractory periods) was also noted in several sites. The large range of recovery intervals found in the present study may suggest that the diencephalon plays an integrative role for rewarding signals arriving from various brain areas.

Animals↗

PubMed1994

Does the MFB convey functionally different reward signals?

Pulse frequencies that sustain the same % of the maximum self-stimulation rate (equipotent frequencies) are equipreferred by rats because they elicit identical reward signals. However, when two equipotent frequencies are delivered through different electrodes, lack of equipreference can be expected if the resulting neural signals belong to different rewarding processes and if these signals are differentially ranked on the animal's decisional scale. We used this rationale to test the possibility that the MFB conveys functionally different signals. Rats were implanted with an electrode near the anterior MFB (aMFB) and another near the posterior MFB (pMFB). The rate of self-stimulation, as a function of the pulse frequency, was first obtained for each electrode, separately. Rats were then allowed to press for aMFB or pMFB stimulation in a double-lever box. One of the levers delivered a fixed aMFB frequency whereas the other delivered a variable pMFB frequency. In the following session, this situation was reversed. The time spent bar-pressing for each stimulus was plotted as a function of the variable frequency. Equipreference for equipotent stimuli (i.e. for frequencies that supported the same % of the maximum rate in the single-lever box) was noted for 6 out of 11 electrode pairs. However, in 3 cases, the subjects preferred the pMFB stimulus over an aMFB equipotent stimulus and in two other cases they preferred the aMFB stimulus. The data from these five subjects suggest the presence of functional heterogeneity within the MFB reward pathway, a view already supported by a variety of other studies.

Animals↗

PubMed1992

Dorsal diencephalic self-stimulation: a movable electrode mapping study.

The function relating electrical self-stimulation (ESS) bar-pressing rate to the frequency of cathodal pulses (0.2 mA and 0.1 ms) was obtained for several positions of a movable electrode in the dorsal diencephalon of the rat. The rate-frequency functions were fitted to a sigmoid model to obtain the asymptotic rate and threshold frequency. ESS was found along the epithalamic route (stria medullaris, habenula, and fasciculus retroflexus) and in the following thalamic nuclei: mediodorsal, paratenial, interanteromedial, centromedial, reuniens, and rhomboid. The lowest threshold (approximately 5 pulses/train), which was found in the stria medullaris and the junction of the paratenial and centromedial nuclei, was comparable to that usually obtained for the brain areas where the ESS is most effectively rewarding (medial forebrain bundle, dorsal raphe, and amygdala). However, most of threshold estimates were 4 to 8 times higher. In most brain sites, ESS was accompanied by epileptiform, motor, or aversive reactions (or a combination of these). These reactions may explain the fact that the maximum rates were generally very low. Nevertheless, no correlation was found between maximum rates and threshold frequencies.

Amygdala↗

PubMed1991

Re-evaluation of the role of dopamine in intracranial self-stimulation using in vivo microdialysis.

Rats were implanted with an electrode-microdialysis assembly in order to test the hypothesis that the reward signal elicited by medial forebrain bundle stimulation is relayed by the meso-accumbens dopamine cells. We first obtained the strength-duration function of self-stimulation, that is, a family of behaviorally equivalent stimuli (pulse intensity and pulse duration pairs yielding a constant self-stimulation rate). We then collected the self-stimulation-bound intra-accumbens dopamine for several pairs of intensity and duration, selected from within the strength-duration function. Our reasoning was that if the reward signal travels along the meso-accumbens dopaminergic neurons, the release of dopamine should not depend on the stimulus parameters because behaviorally equivalent stimuli should produce a constant output in all neural stages carrying the reward signal. The results showed that short duration/high intensity pulses induced considerably larger increases in dopamine levels than long duration/low intensity pulses, despite the fact that these stimuli maintained a constant self-stimulation rate. Among the interpretations envisaged, the most parsimonious one seems to be that the MFB rewarding signal is not relayed exclusively by meso-accumbens dopaminergic cells and that the latter may play a permissive-facilitator role at some transmission stage of the reward signal.

Animals↗

PubMed1991

Interactions between amygdaloid and hypothalamic self-stimulation: a re-examination.

The function relating bar-pressing rate to the frequency of cathodal pulses was obtained in rats self-stimulating with amygdaloid (AMY) and lateral hypothalamic (LH) electrodes. The maximum self-stimulation (SS) rates in the AMY was found to be very low, compared to the LH. Concurrent stimulation with pairs of AMY-LH pulses did not shift the rate-frequency functional laterally, indicating the absence of summation of the two rewarding effects. In a second experiment, concurrent AMY-LH stimulation (using sub-threshold intensity LH pulses) facilitated bar-pressing for AMY stimulation (it increased the slope of the AMY rate-frequency function) without shifting this function laterally. In a third experiment, subjects were given a choice between a pulse frequency yielding maximal AMY rate and a series of higher pulse frequencies. Subjects consistently preferred the higher frequency values, attesting that the maximum AMY rates were not constrained by a saturating reinforcing effect. In a fourth experiment, subjects were given a choice between AMY stimulation and concurrent AMY-LH stimulation, using low intensity LH pulses. Subjects showed no preference for either stimulation condition, although rates were higher for the latter condition. These findings suggest that the maximum rate for AMY stimulation was constrained by factors interfering with bar-pressing and that the effect of these factors was attenuated by co-activation of the LH. In a fifth experiment, pre-treatment with phenobarbital mimicked the rate-enhancing effect of concurrent AMY-LH stimulation for 2 of the 4 subjects tested. This finding suggests that the LH pulses contributed to attenuate seizure activity accompanying AMY SS. In a final experiment, AMY SS rates were also increased by co-activation of rewarding sites in the rostral MFB but not the dorsal raphe, suggesting an anatomical specificity of this effect.

Amygdala↗

PubMed1991

Amygdaloid self-stimulation: a movable electrode mapping study.

The distribution of electrical self-stimulation foci within the amygdala (AMY) was mapped using movable electrodes in rats. Each barpress delivered a 0.4-s train of cathodal rectangular pulses of fixed intensity and duration and variable frequency. The rate-frequency function was recorded for successive dorsoventral sites. Self-stimulation was found throughout the AMY, except in the lateral nucleus. Depending on the site, maximum rates varied from 3 to 37 barpresses/min, whereas threshold frequencies varied from 9.2 to 40 pulses/train; no correlation between these two aspects of self-stimulation was found. Most threshold frequencies lay within the range of 10 to 20 pulses/train, which suggests a relatively homogeneous distribution of rewarding efficacy within the positive areas. The lowest threshold estimates are comparable to those usually obtained for pontine and medial forebrain bundle areas, which suggests that the AMY is an important focus for self-stimulation.

Amygdala↗

PubMed1990

The notion of response invariance in trade-off studies of self-stimulation.

Trade-off profiles, displaying the co-variations of 2 electrical parameters required to maintain a constant magnitude of brain stimulation reward (BSR), have been used extensively in order to characterize the self-stimulation (SS) neurons. It has often been assumed that constancy in the magnitude of BSR can be achieved more accurately by holding SS at a constant proportion of the maximum rate, rather than at a constant rate. The validity of this assumption was tested in 2 experiments using rats. In Exp. 1, we first computed the function that relates SS barpressing rate to pulse frequency (RF function) for two different pulse intensities, separately. The peak SS rate was found to be lower in the low current than in the high current RF function. The rats were then placed in a 2-lever box and were allowed to select either a fixed frequency of the high current pulses or a variable frequency of the low current pulses. In Exp. 2, the RF function was first computed for 2 different lever weights, separately. The peak SS rate was found to be lower in the heavy-lever RF function than in the light-weight lever RF function. The rats were then allowed to select either a fixed pulse frequency delivered by the heavy lever or a variable pulse frequency delivered by the light-weight lever. Isopreference was noted in both experiments, for pulse frequencies which, in the single-lever box, elicited the same proportion of the maximum SS rate, not the same SS rate. The data thus validate the idea that a constant magnitude of BSR is translated into a constant proportion of the maximum SS rate, not a constant SS rate.

Animals↗

PubMed1987

Summation and saturation properties in the rewarding effect of brain stimulation.

We used a two-lever self-stimulation chamber and rats with central grey and hypothalamic electrodes to obtain a choice-frequency (C/F) function, which plots the relative choice of an electrical stimulus of fixed pulse frequency (the standard stimulus) as a function of the frequency of a second competing stimulus (the alternative stimulus). A family of C/F functions was obtained using increasing frequencies for the standard. A choice index, varying from -1.0 (exclusive choice of the fixed stimulus) to 1.0 (exclusive choice of the alternative stimulus) was computed by using the barpressing rates on the two levers. Reward saturation was assumed to occur when the C/F function obtained with the largest standard reached an asymptote below the value of 1.0. For the hypothalamic subjects, the pulse frequency at the point of reward saturation was twice as high as the frequency required for the maximum rate of self-stimulation in the usual single-lever chamber. Decreasing the pulse intensity always increased the saturation frequency, indicating that the saturation was not due to a frequency blocking effect in the directly activated neurons. Reward saturation occurred with a considerably higher frequency in the central grey than in the hypothalamus. Thus, the asymptotic rate of self-stimulation in the usual single-lever chamber is not conditioned by the processes that summate the central grey and hypothalamic rewarding effects. From the central grey data we obtained the relation between the slope and the position of the C/F function on the frequency axis. We used the slope/frequency profile to delimit the most probable profile of summation rate in the rewarding process. We found that the slope/frequency function has an early plateau followed by a rapidly decelerating phase. We proposed that these two distinct phases reflect an early accelerating rate of summation, followed by a decelerating rate of summation. In other words, reward summation would be predicted by a sigmoid growth model.

Animals↗

PubMed1987

Behavioral determination of refractory periods of the brainstem substrates of self-stimulation.

The objective of this study was to estimate the refractory periods of the brainstem neurons responsible for self-stimulation behavior in the rat. In a first experiment, we tested the robustness of the double pulse technique used to estimate the refractory periods of reward-relevant neurons. We obtained estimates of the relative T-pulse effectiveness at a wide range of stimulation frequencies. The results of this experiment suggest that the refractory period estimates obtained with the behavioral version of the double pulse technique are not dependent on the arbitrary choice of the stimulation frequency. However, the use of stimulation frequencies higher than 100 Hz should preferably be avoided. In a second experiment, we applied the double pulse technique using C-pulse intensity higher than T-pulse intensity to estimate the refractory periods of the brainstem reward-relevant neurons. Using moveable electrodes, we tested 9 metencephalic and 7 mesencephalic sites in 4 animals. In the metencephalon, the most excitable reward-relevant neurons have absolute refractory periods of less than 0.6 and 0.8 ms and have a supernormal period that occurs at least between 5 and 10 ms after the initial excitation. The mesencephalic reward-relevant neurons were found to have more heterogeneous physiological characteristics. The most excitable cells in the mesencephalon have absolute refractory periods of less than 0.4 ms and have a supernormal period occurring as soon as 2.4 ms after the initial excitation. At some mesencephalic sites, we observed first an abrupt initial recovery followed by a plateau, followed by a renewed and continuous recovery, a pattern that was never observed in the metencephalon. The hypothesis of the contribution of two distinct sub-populations of reward-relevant neurons is proposed and the implication of monoaminergic pathways in reward is discussed.

Animals↗

PubMed1987

Anatomical dissociation of the substrates of medial forebrain bundle self-stimulation and exploration.

The purpose of this research was to determine whether brain stimulation reward and exploration are induced by activation of the same set of neurons along the medial forebrain bundle. The behavioral version of the collision test was utilized with electrodes in the lateral hypothalamus (LH) and the ventral tegmental area (VTA). A collision effect obtained between LH and VTA in one behavior at the exclusion of the other was treated as evidence of the involvement of two different sets of fibers. In 4 rats, a collision effect was observed only in self-stimulation, whereas in 1 rat, a collision was obtained in exploration at the exclusion of self-stimulation. Three animals showed no collision in either behavior. These data suggest that coexistence of self-stimulation and exploration following medial forebrain bundle stimulation can be explained by current spread on two different sets of fibers.

Animals↗

PubMed1987

Fitting intracranial self-stimulation data with growth models.

Until now, the problem of fitting self-stimulation rate-frequency functions has been dealt with by using linear models applied to the linear portion of the empirical curve. In this article, an alternative procedure is presented, together with three sigmoid growth models that seem to accurately fit rate-frequency data. From any of these models, it is possible to compute the two indices of stimulation efficacy in use in the parametric study of brain stimulation reward (M50 and theta 0), in addition to the inflection point of the curve, which can be used as an alternative to M50. Important relations allowing initial estimation of each parameter are provided, allowing use of computer programs derived from the Gauss-Newton algorithm for nonlinear regression. The considerations relevant to the choice of a nonlinear model are discussed in terms of each efficacy index.

Algorithms↗