Microbial degradation of tetraethyl lead in soil monitored by microcalorimetry

Fos immunohistochemistry was used to stain neurons in the caudal diencephalon, midbrain and hindbrain driven by rewarding stimulation of the lateral hypothalamus (LH). Increases in Fos-like immunoreactivity were most pronounced ipsilateral to the site of stimulation and tended to be confined within discrete structures such as the posterior LH, arcuate nucleus, ventral tegmental area (VTA), central gray, dorsal raphé, pedunculopontine area (PPTg), parabrachial nucleus, and locus coeruleus. At least two of these structures, the VTA and PPTg, have been implicated in medial forebrain bundle self-stimulation.     

Self-stimulation of the habenular complex in the rat.

65 male hooded Long-Evans rats learned to barpress for rewarding electrical stimulation of the medial or lateral habenular nucleus or the fasciculus retroflexus, but not the surrounding thalamic nuclei. Response rates were moderate and steady and were not influenced by food or water deprivation. Habenular self-stimulation was significantly facilitated by placing lesions in the ipsilateral anterior part of the medial forebrain bundle (MFB). Similarly, MFB self-stimulation was enhanced by ipsilateral habenular lesions. Lesions centered in the region of median raphe nucleus suppressed habenular self-stimulation for more than 4 wks. Self-stimulation of median raphe was not affected by habenular lesions. Results show that habenular stimulation can produce a rewarding effect by exciting neurons in the region of the raphe nuclei but apparently without requiring the participation of the well-known MFB reward system. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pain-reducing properties of rewarding electrical brain stimulation in the rat.

In 4 experiments with 13 male Charles River rats, electrodes implanted along the medial forebrain bundle were screened for self-stimulation and stimulation-induced analgesia. Analgesia was defined by changes in unconditioned or escape responses to footshock. Almost all electrodes produced both self-stimulation and analgesia or neither. Thresholds for the 2 effects were highly correlated. Brain stimulation produced an analgesic aftereffect comparable in duration with the poststimulation enhancement of performance in self-stimulation (the priming effect). The refractory period of neurons underlying analgesia, assessed by behavioral means, was similar to that previously found for the priming effect in self-stimulation (.8-1.2 msec). Results suggest a common neural system mediating electrical analgesia and the priming effect of self-stimulation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased ipsilateral expression of Fos following lateral hypothalamic self-stimulation

Immunohistochemical labeling of Fos protein was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic level of the medial forebrain bundle (MFB). Following training and stabilization of performance, seven rats were allowed to self-stimulate for 1 h prior to anesthesia and perfusion. Brains were then processed for immunohistochemistry. Two control subjects were trained and tested in an identical manner except that the stimulator was disconnected during the final 1 h test. Among the structures showing a greater density of labeled neurons on the stimulated side of the brains of the experimental subjects were the septum, lateral preoptic area (LPO), medial preoptic area, bed nucleus of the stria terminalis, substantia innominata (SI), and the lateral hypothalamus (LH). Several of these structures, the LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of psychophysical, electrophysiological, and lesion studies.     

Self-stimulation in 7- and 10-day-old rats.

It has been shown that the infant rat exhibits learned behaviors characteristic of the adult. With a modified self-stimulation paradigm, the present study explored whether 7- and 10-day-old Long-Evans rat pups could learn a discriminated operant to obtain direct electrical stimulation in neural sites that support self-stimulation in adults. By nudging 1 of 2 response manipulanda, at 2 ages (7 and 10 days) and temperatures (22 and 35°C), Ss self-stimulated with electrodes implanted in a variety of forebrain sites, including the prefrontal cortex, bed nucleus of the stria terminalis, medial nucleus of the amygdala, and the medial forebrain bundle. The only temperature-sensitive site might be the nucleus accumbens, which was positive only at the higher temperature in 10-day-olds. Results indicate that several forebrain sites demonstrate rewarding properties of stimulation in the preweanling rat pup. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessment of the neural substrate for intracranial self-stimulation by the postreinforcement pause technique.

The poststimulation excitability of neurons mediating intracranial self-stimulation (ICSS) was evaluated by the paired-pulse method. Stimulus effectiveness was assessed by the postreinforcement pause (PRP) and by frequency threshold (FT) determinations in 7 rats performing ICSS in the medial forebrain bundle (MFB) and in the ventral tegmental area (VTA). Stimulus effectiveness values were minimal at conditioning-test (C-T) pulse intervals of 0.6 and 0.8 ms for MFB and VTA animals, respectively, because of neuronal refractoriness. Local potential summation could account for the increase in effectiveness at very short C-T intervals, and an additional peak of enhanced effectiveness at a C-T interval of 2.0 ms, perhaps reflecting synaptic events, was observed only in VTA animals with the PRP method. Important advantages of the PRP method were that the C-T interval was the only stimulus parameter that was varied, and the behavioral output of the animal remained relatively constant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Destruction of the medial forebrain bundle caudal to the site of stimulation reduces rewarding efficacy but destruction rostrally does not.

Rats with an electrode in the medial forebrain bundle (MFB) in or near the ventral tegmental area and another at the level of the rostral hypothalamus sustained large electrolytic lesions at either the rostral or the caudal electrode. The rewarding efficacy of stimulation through the other electrode was determined before and after the lesion. Massive damage to the MFB in the rostral lateral hypothalamus (LH) generally had little effect on the rewarding efficacy of more caudal stimulation, whereas large lesions in the caudal MFB generally reduced the rewarding efficacy of LH stimulation by 35–60%. Similar reductions were produced by knife cuts in the caudal MFB. These results appear to be inconsistent with the hypothesis that the reward fibers consist either of descending or ascending fibers coursing in or near the MFB. It is suggested that the reward fibers are collaterals from neurons with both their somata and their behaviorally significant terminals located primarily in the midbrain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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-sec 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine release in the nucleus accumbens by hypothalamic stimulation-escape behavior

It is known that lateral hypothalamic stimulation or self-stimulation can release dopamine in the nucleus accumbens (NAc). The present experiment illustrates that an aversively motivated behavior can also do this. Rats were prepared with microdialysis probes in the NAc and electrodes in the lateral hypothalamus (LH) or medial hypothalamus (MH). Automatic stimulation of the LH increased extracellular dopamine in the NAc 30% as reported earlier. The animals would perform both self-stimulation to turn the current on and stimulation-escape to turn it off, suggesting a combination of reward and aversion. Escape responding increased extracellular dopamine (DA) 100%, even though there was less total stimulation. Automatic stimulation of the MH did the opposite of the LH by decreasing accumbens dopamine (-20%), and the animals would only perform stimulation-escape, indicative of pure aversion. But again, extracellular DA in the NAc increased 100% during escape responding. Thus DA can be released during negative reinforcement when an animal's behavior is reinforced by escape from lateral or medial hypothalamic stimulation. This suggests that DA release was correlated with stimulation-escape behavior, rather than the aversiveness of automatic stimulation.     

Conditioned suppression of medial forebrain bundle and septal intracranial self-stimulation in the rat: Evidence for a fear-relief mechanism of the septum.

In 3 experiments, a conditioned emotional response (CER) paradigm was presented to 2 groups of male albino Sprague-Dawley rats (N?=?20) during intracranial self-stimulation (ICSS). One group barpressed for medial forebrain bundle (MFB) stimulation reward; the other group barpressed for septal stimulation reward. The MFB ICSS was found to be suppressed by the CER procedure, but this procedure failed to suppress septal ICSS. The difference between the 2 sites was found only when both MFB and septal ICSS current intensities were available at their optimal levels. When ICSS current intensities were lowered to either threshold or medium level, both groups exhibited the CER suppression effect. Ss were also tested for a possible analgesic effect produced by the ICSS. MFB stimulation was found to produce some degree of analgesia, but septal stimulation failed to produce any analgesic effect. Thus, the possibility that the attenuation of the CER suppression effect in the septal group was due to analgesia was excluded. The difference in MFB and septal ICSS behavior during the presentation of the aversive stimulus suggests a possible qualitative distinction between the reward functions of the 2 sites, and a possible fear-reduction property of the septal area. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A neuroanatomical investigation of enhanced cutaneous and gustatory responsivity associated with septal forebrain injury.

Observed enhanced reactivity to cutaneous stimulation (handling and footshock) in 14 male Sprague-Dawley rats sustaining either large septal lesions or medial forebrain bundle ablations at the level of the septum. Cutaneously elicited hyperreactivity was not noted in 7 unoperated controls or 28 Ss with smaller septal lesions placed in the anterior, posterior, or dorsal septum or with lesions in the stria terminalis. All septal ablations but neither the medial forebrain bundle nor the stria terminalis lesions produced a gustatory hyperreactivity in the form of altered intakes of quinine and saccharin solutions. The gustatory hyperreactivity to quinine was clearly maximal in Ss with posterior ventral septal injury. Significantly, this lesion always extended into the medial preoptic nucleus. These results point to different neuroanatomical mechanisms in the septum underlying cutaneous- vs. gustatory-elicited behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Voltammetry of extracellular dopamine in rat striatum during ICSS-like electrical stimulation of the medial forebrain bundle

Fast-scan cyclic voltammetry in the striatum of anesthetized rats has been used to monitor extracellular dopamine during forced electrical stimulation of the media forebrain bundle using parameters that mimic intracranial self-stimulation. The temporal resolution provided by microelectrodes positioned very near sites of dopamine release allows resolution of the response to individual 500-ms stimulation trains separated by 500-ms intervals. Uptake inhibition by Nomifensine alters the resolution obtained at short times after initiation of stimulation.     

Does the perception of reward magnitude of self-administered electrical brain stimulation have a circadian rhythm?

The locus of rise of the rate-frequency function was determined for rats at many times of day to ascertain whether the circadian fluctuations in the frequency of bar pressing for electrical stimulation of the medial forebrain bundle could be accounted for by alterations in the perceived magnitude of the reward. No evidence of circadian changes in the value of the locus of rise were detectable. These findings suggest that for self-stimulation, the endogenous circadian rhythm generating apparatus affects behavior through neural mechanisms similar to those through which motivational and arousal variables act. The animal's requirement for verity of memorial representations may underlie the lack of circadian rhythm in the locus of rise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mesencephalic THmRNA-reduced expression by blocking axonal transport with colchicine

Colchicine, an axonal transport blocking agent, was unilaterally injected in the medial forebrain bundle of rats. As early as 18 h after the injection a rapid decrease in TH-mRNA level was observed in the substantia nigra and the ventral tegmental area (SN/VTA) on the injected side. In contrast, TH protein levels remained stable for 48 h, and decreased later in both cells bodies and terminals (caudate/putamen). The number of TH-immunopositive cells in SN/VTA increased after colchicine equally in both sides, excluding a neurotoxic effect. These results suggest that TH gene expression is controlled by a retrogradely transported activating factor rather than by feedback inhibition by the end product, i.e. TH protein.     

Effects of a single administration of clozapine on mouse brain catecholamines

In acute experiments on cats anesthetized with nembutal and chloralose the projections of different parts of orbito-frontal cortex, basal temporal cortex and hippocampus to hypothalamic nuclei were studied by focal potential recording. It was found that the proreal gyrus has local projections into the latero-dorsal parts of the preoptical region, rostral parts of the forebrain medial bundle, lateral and posterior hypothalamus with mammilary bodies. The orbital gyrus is projected mainly into latero-dorsal parts of the forebrain medial bundle, latero-ventral part of the preoptical region, and the region of lateral and latero-dorsal hypothalamic nuclei. Projections from the orbital gyrus are of a relatively diffuse character. The basal temporal cortex has diffuse projections into the central part of the preoptical region, latero-ventral part of the forebrain medial bundle and lateral mammilary body. No pronounced foci were observed in the hypothalamic structures during stimulation of the hyppocampus, but diffuse projections were found into ventral parts of the preoptical region and ventral regions of the forebrain medial bundle as well as into lateral hypothalamus and lateral mammilary nucleus.     

Lesions of pontomesencephalic cholinergic nuclei do not substantially disrupt the reward value of medial forebrain bundle stimulation

This study examines the effects of lesioning the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) on the reward effectiveness of medial forebrain bundle (MFB) stimulation. Although the focus is on the effects of unilateral lesions made ipsilateral to stimulation sites in the hypothalamic and ventral tegmental MFB, the effects of contralateral lesions of both targets are also investigated. Reward effectiveness was assessed using the rate-frequency curve shift paradigm. In nine rats with unilateral PPTg lesions and five rats with unilateral LDTg lesions, the frequency required to maintain half-maximal response rats was generally not changed by more than 0.1 log units relative to prelesion baseline mean. In three rats with contralateral PPTg lesions and four rats with contralateral LDTg lesions, required frequency was also not substantially changed. The results are interpreted in terms of a previously proposed hypothesis regarding the role in MFB self-stimulation of ascending cholinergic input from the pontomesencephalon to ventral tegmental dopaminergic neurons.     

Contribution of ventral tegmental area dopamine neurons to expression of conditional fear: Effects of electrical stimulation, excitotoxin lesions, and quinpirole infusion on potentiated startle in rats.

Potentiated startle was used in this study to determine the fear-motivational functions of the ventral tegmental area (VTA) in rats. In Experiment 1, electrical stimulation of the VTA increased acoustic startle amplitudes. In subsequent experiments fear-potentiated startle was assessed following axon-sparing N-methyl-D-aspartate (NMDA) lesions of the VTA and after bilateral intra-VTA infusion of the dopamine (DA) D2/3 receptor agonist quinpirole. The NMDA lesions produced substantial cell loss in the medial ventral tegmentum and suppressed fear expression. Similarly, inhibition of DA neuronal activity associated with locally administered quinpirole blocked fear-potentiated startle. It was suggested that VTA neurons and their forebrain DA projections regulate levels of aversive emotional arousal within the amygdala-based fear system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of knife-cut lesions of the medial forebrain bundle in self-stimulating rats.

Unilateral frontal-plane knife-cut lesions were made in the anterior medial forebrain bundle ipsilateral to a lateral hypothalamic self-stimulation electrode. Behavioral effects of the knife cut on self-stimulation reward and operant performance capacity were measured via the reward summation function method. Knife cuts placed at the level of the anterior commissure were ineffective in altering reward or motor/performance capacity, whereas knife cuts just posterior in the caudal lateral preoptic area degraded reward and sometimes impaired motor/performance capacity. In a second experiment, knife cuts placed posterior to the ventral tegmental area were ineffective unless they intruded on the ventral tegmental area itself. Several small knife cuts placed just anterior to the ventral tegmental were effective in reducing self-stimulation reward. The results are discussed in terms of the anatomical substrate of lateral hypothalamic self-stimulation reward and as a first step in a larger mapping study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporary inactivation of ventral tegmental area neurons with either muscimol or baclofen reversibly disrupts maternal behavior in rats through different underlying mechanisms.

The purpose of this study was to examine the effects of inactivation of ventral tegmental area (VTA) projection neurons, while sparing fibers of passage, on maternal behavior in rats. Because VTA neurons contain GABA-A and GABA-B receptors, the effects of muscimol or baclofen were studied. Although bilateral injections of either drug into the VTA disrupted maternal behavior, it is likely that they did so through different underlying mechanisms. Muscimol disrupted both retrieval of pups and nursing behavior, while causing stereotyped motor activity. Baclofen disrupted retrieval behavior without affecting nursing behavior, and control injections of baclofen into the region dorsal to VTA were ineffective. The effects of VTA baclofen on maternal behavior are similar to the effects of interference with mesolimbic dopamine (DA) function. The case is made that muscimol probably caused a hyperexcitation of VTA DA neurons through a process of disinhibition. In contrast, baclofen may have depressed the activity of all VTA projection neurons, including VTA DA neurons. Baclofen is a promising tool to explore whether medial preoptic area neurons interact with VTA neurons to control active maternal responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)