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)     

Deficient passive and one-way active avoidance acquisition following medial forebrain bundle lesions in rats.

In 3 experiments with 93 Long-Evans male hooded rats, cathodal electrolytic lesions of the medial forebrain bundle (MFB) at posterior hypothalamic levels produced a mild, transient hypodipsia and lowered jump thresholds to footshock. Lesions produced marked deficits in passive avoidance performance in a paradigm that paired discrete, linearly incrementing footshock intensities with contact of a water spout following 48 hrs of water deprivation. Injections of levo-dextro-5-hydroxytryptophan (75 mg g, ip), the immediate metabolic precursor of serotonin, had no effect on the passive avoidance performance of either experimental or operated control Ss. Lesions of the MFB also resulted in deficient acquisition in a 1-trial step-through passive avoidance paradigm not using motivation to drink and caused a severe acquisition deficit in a 1-way active avoidance task. Lesions of the septal nuclei produced lowered jump thresholds but did not affect acquisition in the 1st passive avoidance task. Results are interpreted as indicating a lesion-induced deficiency in fear learning, independent of the serotonergic functions of the MFB. (45 ref) (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.     

Altered sensitivity to footshock after selective serotonin depletion: Comparison of electrolytic lesions and neurotoxin injections in the medial forebrain bundle of the rat.

Compared the changes in 183 male albino rats' jump threshold with changes in monoamine content of the telencephalon after damage to the lateral hypothalamus produced either by electrolytic lesions or by 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (DHT). Electrolytic lesions produced significant decreases in jump threshold and in telencephalic content of serotonin, norepinephrine, and dopamine. Infusions of DHT, with or without pretreatment with desipramine, always reduced both jump thresholds and serotonin content, even when there was no effect on norepinephrine or dopamine. In contrast, 6-OHDA had no effect on jump thresholds or serotonin content, even though both norepinephrine and dopamine were greatly reduced. Results suggest that the increased sensitivity to footshock was solely due to the interruption of ascending serotonergic pathways within the lateral hypothalamus and was not a result of damage either to norepinephrine and dopamine pathways or to some other neural system. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of rostral medial forebrain bundle and olfactory tubercle lesions upon sexual behavior of male rats.

Examined the effect on sexual behavior of 57 male Sprague-Dawley rats of reduced olfactory system input to the preoptic area and medial forebrain bundle (MFB). Bilateral electrolytic lesions in the MFB just caudal to the preoptic area virtually abolished mating behavior. Electrolytic lesions or sham lesions placed bilaterally in the olfactory tubercle produced decrements in the mating behavior. There was no evidence of gonadotropic dysfunction in any of the groups, nor were there significant differences in their mean body weights at sacrifice. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

Electrolytic lesions of the cortical and adjacent nuclei in the amygdala differentially influence thresholds for rewarding medial forebrain bundle stimulation.

After electrolytic lesions to the cortical and adjacent amygdaloid subnuclei, thresholds for rewarding medial forebrain bundle (MFB) stimulation were tracked in 19 rats with bilateral implants and 8 with single implants. Results were categorized into 3 groups depending on the magnitude of the lesion effect on ipsilateral frequency thresholds: substantial (> 60%), small (> 26%), or none (     

Prolonged rewarding stimulation of the rat medial forebrain bundle: Neurochemical and behavioral consequences.

Extracellular dopamine levels were measured in the rat nucleus accumbens by means of in vivo microdialysis. Delivery of rewarding medial forebrain bundle stimulation at a low rate (5 trains/min) produced a sustained elevation of dopamine levels, regardless of whether train onset was predictable. When the rate of train delivery was increased to 40 trains/min, dopamine levels rose rapidly during the first 40 min but then declined toward the baseline range. The rewarding impact of the stimulation was reduced following prior delivery of stimulation at the high, but not the low, rate. These results support the idea that dopamine tone plays an enabling role in brain stimulation reward and is elevated similarly by predictable and unpredictable stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

The effect of anterior lesions to the medial forebrain bundle on the motor activity evoked by a sensory deficit (sensory drive) in rats]

The orbito-frontal cortex and postcommissural MFB lesions evoked two major effects. The first one consisted in an increased need for light stimulation while the second one concerned changes in anxiety level with different results depending on the lesion location (cortical ot subcortical). The second effect is in agreement with P. Simonov's hypothesis concerning the different configurations of the CNS structures. Upon destruction of the orbito-frontal area, the dominant role in behaviour regulation is taken over by the "emotional part" of the brain, whereas the destruction of the postcommissural MFB (reduction of the amygdalar influence on the hypothalamus) creates conditions for functional prevalence of the "informational brain".     

Increased expression of NGFI-A mRNA in the rat striatum following burst stimulation of the medial forebrain bundle

Using in situ hybridization, we examined the mRNA expression for several immediate early genes in dopamine-innervated brain areas following electrical burst vs. regular stimulation of the medial forebrain bundle in anaesthetized rats. Two hours after 5 Hz burst stimulation, the expression of the nerve growth factor-inducible clone A (NGFI-A) mRNA was increased in the medial part of the striatum. This increase was prevented by pretreatment with the dopamine-D1 receptor antagonist, SCH23390 (0.1 mg/kg i.p.). After 8 Hz burst stimulation, NGFI-A mRNA expression was increased in the medial, central and lateral parts of the striatum. Induction occurred predominantly in cells expressing mRNAs for the dopamine-D1 receptor, substance P and dopamine and cAMP-regulated phosphoprotein (DARP-32). Regular stimulation had no effect on NGFI-A mRNA expression. The induction of NGFI-A was related to the levels of dopamine released by burst or regular stimulation as demonstrated with in vivo amperometry. Two hours after stimulation, the expression of none of the other genes studied was altered. One hour after 8 Hz burst stimulation, the expression of NGFI-A, NGFI-B and jun-B mRNAs was increased in the striatum and that of NGFI-A, NGFI-B, c-fos, fos-B and jun-B mRNAs was variably increased in the nucleus accumbens and lateral septum. These results provide additional support for the physiological importance of burst firing activity in midbrain dopamine neurons for the activation of their target cells. They demonstrate a spatial and temporal specificity as regards the brain region, the gene activated, the receptor involved and the phenotype of the cells affected.     

Medial forebrain bundle lesions: Specific loss of feeding to decreased glucose utilization in rats.

Found that bilateral destruction of the medial forebrain bundle in female Sherman rats eliminated feeding to decreased intracellular glucose utilization (glucoprivation). The deficit was specific. Feeding was enhanced by dietary dilution and reduced by dietary concentration. More was eaten in the cold and less in the heat. The Ss were not differentially sensitive to quinine adulteration. They returned to normal body weight following regimens of gavage or of restricted feeding. Moreover, they did not differ from normal Ss in drinking to various thirst stimuli. It is suggested that the glucoprivic mechanism makes but a minor contribution to the initiation of spontaneous feeding. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

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.     

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)     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of inferior colliculus lesions on the acoustic startle response.

"Nonspecific" electrolytic lesions (with respect to subdivision) of the mouse inferior colliculus (IC) resulted in the attenuation of acoustic startle response (ASR) amplitudes of the 1st postoperative day, but ASR amplitudes increased to above baseline levels 1 wk later. Lesions of the IC central nucleus (CN) also attenuated ASR amplitudes on the 1st postsurgery day, but startle amplitudes recovered to baseline levels 1 wk after surgery. Lesions of the IC lateral nucleus (LN) or dorsal cortex (DC) resulted in elevation of startle amplitudes above baseline 7 days after surgery and produced enhanced ASR amplitudes to repeated stimuli. 14 days after the surgery, lesion effects on startle amplitudes remained the same as those on Day 7 for each lesion condition. The present findings implicate the ICLN and ICDC as inhibitory modulators of the ASR, but indicate only a minor role for the ICCN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the medial geniculate body in prepulse inhibition of acoustic startle

Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABA(B) receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABA(A) receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.     

The effect of medial and lateral lesions in the amygdala on fixed-ratio performance.

Trained 18 male albino Wistar rats with medial or lateral lesions in the amygdala to respond on progressively increasing fixed-ratio schedules of reinforcement. Results indicate that medial lesions produced an earlier breakdown of responding, and lateral lesions produced perseveration of response. Interpretations of the data in terms of motivational effects and excitatory and inhibitory functions are discussed. (French summary) (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdaloid block fear-potentiated startle and shock sensitization of startle.

Destroyed cell bodies in the lateral and basolateral amygdaloid nuclei by local infusion of N-methyl-{d}-aspartate. Adjacent areas, such as the central amygdaloid nucleus, were largely spared. Lesions were carried out before training and testing (Exp 1) or after training but before testing (Exp 2). In both cases, the lesions completely blocked fear-potentiated startle (increased acoustic startle in the presence of a light previously paired with footshock). They also blocked increased startle after a series of footshocks, provided they damaged the most anterior part of the basolateral nucleus. It is suggested that the lateral or basolateral amygdaloid nuclei (or both) relay visual information to the central amygdaloid nucleus, which is also critical for fear-potentiated startle. In addition, activation of the most anterior part of the basolateral nucleus may be critical for processing shock information during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)