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Unilaterally activated systems in rats self-stimulating at sites in the medial forebrain bundle, medial prefrontal cortex, or locus coeruleus.

Rats with electrodes in either the posterior medial forebrain bundle (MFB), the anterior MFB, the medial prefrontal cortex, or the locus coeruleus self-stimulated during a 45 min period following the injection of [14C]2-deoxyglucose. They were then sacrificed and their brains prepared for autoradiography. The autoradiographs were analyzed for unilaterally activated neural systems, using a computerized image analyzing system to compare the darkness of neural structures on the stimulated side with the darkness of the same structures on the unstimulated side. There was extensive overlap in the neural structures unilaterally activated by stimulation in the anterior and posterior MFB; but there was no overlap between the structures activated by MFB stimulation and the structures activated by stimulation at either of the extradiencephalic sites; nor did the forebrain, diencephalic, and midbrain sites have any readily apparent bilateral effects in common. If there is a substrate common to MFB self-stimulation and extradiencephalic self-stimulation, its activation is not revealed by 2-deoxyglucose autoradiography.

Animals

Light and electron microscopic studies on the medial forebrain bundle in rat: III. Degenerated nerve elements in the medial hypothalamic nuclei following surgical transections of the medial forebrain bundle.

Transections of the rat medial forebrain bundle at various levels and the separation of the medial and lateral hypothalamus were performed to study with light and electron microscopy axonal and terminal degeneration in the arcuate, ventromedial and dorsomedial nuclei and in the median eminence. Fibres entering the MFB from various directions participate in the innervation of the arcuate nucleus. The bulk of extrahypothalamic fibres terminating in the median eminence derive from the lower brain stem and reach their target through the MFB. Preoptic originating and transient fibres also terminate in the median eminence. Following parasagittal separation of the medial and lateral hypothalamus massive degeneration was found in both layers of the median eminence. This is likely to be due to interruption of the supraoptic-hypophyseal tract but axons of intrinsic MFB-neurons might also contribute to the innervation of the median eminence.

Animals

Medial forebrain bundle of the rat: III. Cytoarchitecture of the rostral (telencephalic) part of the medial forebrain bundle bed nucleus.

The boundaries of the medial forebrain bundle (MFB) of the rat have been presented in previous work on the structure of this fiber system (Nieuwenhuys et al.: J. Comp. Neurol. 206:49-81, '82). Neuronal cell bodies within these outlines constitute the bed nucleus of the MFB. Many fiber components of the MFB appeared to be spatially arranged within the bundle and featured an orderly topography (Veening et al.: J. Comp. Neurol. 206:82-108, '82). As the fibers of the MFB are thought to be a major source of afferents to the bed nucleus (Millhouse: In P.J. Morgane and J. Panksepp (eds): Anatomy of the Hypothalamus, Vol. 1. New York: Marcel Dekker, pp. 221-265, '79), the latter has been subjected in this and the companion study (Geeraedts et al.: J. Comp. Neurol. 294:537-568, '90) to a detailed cytoarchitectonic analysis. This analysis is based on continuous series sectioned in the three conventional planes. On the basis of cytoarchitectonic characteristics, including size and shape, staining intensity, packing density, and spatial orientation of the cell bodies, it was found that the bed nucleus of the MFB as described in the literature is by no means a cytoarchitectonic unit per se. Rather, the neuronal cell population located within the telencephalic stream of the MFB can be parcellated into a number of cellular groups, which partly or entirely belong to more-or-less known basal telencephalic structures. These structures are designated here as the MFB-related areas. They correspond largely to the subcommissural substantia innominata (SIC), the sublenticular substantia innominata (SIL), the nucleus of the diagonal band of Broca, the olfactory tubercle, the magnocellular preoptic nucleus (POMA), the lateral preoptic area (LPOA), and the interstitial nucleus of the stria medullaris (ISM). The complex of the MFB-related areas is surrounded by the following cellular entities: the nucleus accumbens (ACB), the caudatus-putamen region (CPU), the globus pallidus (GP), the bed nucleus of the stria terminalis (BST), the anterior amygdaloid area (AAA), the amygdaloid nuclear complex (A), the medial preoptic area (MPOA) and the anterior hypothalamic area (AHA). Both MFB-related areas and their surroundings have been identified and delimited in this study. This resulted in a new cytoarchitectonic atlas of the rat's basal telencephalon. Our atlas does not only show the relative positions of the above mentioned cellular groups, but also those of their subdivisions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Medial forebrain bundle of the rat: IV. Cytoarchitecture of the caudal (lateral hypothalamic) part of the medial forebrain bundle bed nucleus.

In the preceding study (Geeraedts et al.: J. Comp. Neurol. 294:507-536, '90), the rostral or telencephalic portion of the rat's bed nucleus of the medial forebrain bundle (MFB) has been parcellated into several cytoarchitectonically distinct cellular groups and subgroups. The purpose of the present investigation is to subject the caudal or lateral hypothalamic (LH) portion of the MFB bed nucleus to a detailed cytoarchitectonic analysis. This analysis is based on the same materials, methods, and cytoarchitectonic criteria that were also employed in the preceding study. In contrast to descriptions in the literature, it was found that the LH-region constitutes a very heterogeneous population of neurons with an evident arrangement into groups, several of which have not been identified previously. Many of these cellular groups are partly or entirely located within the boundary of the LH-trajectory of the MFB as previously established by Nieuwenhuys et al. (J. Comp. Neurol. 206:49-81, '82). These groups are designated here as the MFB-related cellular groups. They appear to be arranged into two longitudinal zones. Both zones are caudally replaced by the ventral tegmental area (VTA) and a part of the mesencephalic tegmentum (TEGM1). The lateral zone lies in close proximity to the internal capsule/cerebral peduncle and comprises the following cellular groups: the ventrolateral subarea of the lateral hypothalamic area (LHVL), the anterolateral subarea of the lateral hypothalamic area (LHAL), the lateral tuberal nucleus (TUL), the pre-subthalamic nucleus (PSUT), the retro-subthalamic nucleus (RSUT), the anterodorsal subarea of the lateral hypothalamic area (LHAD), and the lateral hypothalamic nucleus (LHN). The medial zone consists of the following cellular groups: the intermediate hypothalamic area (IHA), the medial tuberal nucleus (TUM), the perifornical nucleus (PFX), the lateral supramammillary nucleus (SUL), the submammillothalamic nucleus (SMT), and the nucleus geminus posterior (GEP). The cellular groups of the medial zone together with the tuberomammillary nucleus groups of the medial zone together with the tuberomammillary nucleus (TUMM) are positioned at the interface between the lateral and the medial hypothalamus, and form an array of cellular groups indicated in our study as the intermediate division of the hypothalamus. The MFB-related cellular groups are dorsally, medially, ventrally, and laterally surrounded by rather well-known brain structures. Both the MFB-related cellular groups and the surrounding structures have been identified and delimited. This resulted in a new, elaborate cytoarchitectonic atlas of the rat's lateral hypothalamic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Chronic intranigral administration of brain-derived neurotrophic factor produces striatal dopaminergic hypofunction in unlesioned adult rats and fails to attenuate the decline of striatal dopaminergic function following medial forebrain bundle transection.

The present study determined the effects of chronic intranigral injections of recombinant human brain-derived neurotrophic factor (1 micrograms) every second day for 19 days on the functional capacity of dopaminergic neurons of the nigrostriatal pathway of unlesioned adult rats. In animals chronically treated with brain-derived neurotrophic factor, we observed amphetamine (5 mg/kg)-induced circling behavior directed toward the neurotrophin-injected side (33 turns/5 min). The behavioral asymmetry was paralleled by reductions of striatal [3H]dopamine uptake (27%), tyrosine hydroxylase activity (68%), dopamine content (36%) and [3H]mazindol binding site density (35%) on the same side as brain-derived neurotrophic factor treatment. While chronic injections of brain-derived neurotrophic factor produced a modest decrease in the number of tyrosine hydroxylase-positive cell bodies in the vicinity of the injection site, a similar reduction in cell number was observed in animals injected with a control protein, cytochrome c. However, in contrast to the animals treated with brain-derived neurotrophic factor, rats treated with the control protein showed no amphetamine-induced circling behavior, and there were no significant reductions in neurochemical parameters of striatal dopaminergic function. Lastly, we found that in brain-derived neutrophic factor-injected animals there was a 30% decrease of tyrosine hydroxylase messenger RNA levels in the ventral mesencephalon. We also determined the effects of brain-derived neurotrophic factor treatment on animals with transections of the medial forebrain bundle. Medial forebrain bundle-lesioned animals challenged with amphetamine circled (55 turns/5 min) ipsilateral to the lesioned side. The medial forebrain lesions decreased the following markers of striatal dopaminergic function: [3H]opamine uptake (65%), tyrosine hydroxylase activity (79%), dopamine content (80%) and [3H]mazindol binding site density (52%), induced a pronounced loss of tyrosine hydroxylase-positive cell bodies within the substantia nigra and also reduced tyrosine hydroxylase messenger RNA levels. Chronic intranigral brain-derived neurotrophic factor treatment did not attenuate nor did it exacerbate the medial forebrain bundle lesion-induced decreases of dopaminergic parameters in either the substantia nigra or striatum. The results of the present study indicate that chronic intranigral administration of brain-derived neurotrophic factor to normal adult rats induces a dopaminergic hypofunction in the striatum which is manifested behaviorally by amphetamine-induced rotations. The brain-derived neurotrophic factor-induced striatal function is not the result of significant cell loss at the levels of the substantia nigra, but seems to be related to brain-derived neurotrophic factor-induced down-regulation of dopaminergic-specific proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamine

Regional differences in desensitization of c-Fos expression following repeated self-stimulation of the medial forebrain bundle in the rat.

The acute self-stimulation of the medial forebrain bundle was reported to induce the expression of c-Fos, the protein product of c-fos, an immediate early gene, in the central nervous system. In the present study, we examined regional changes in c-Fos expression in several reward-related areas of rat brain in response to short- and long-term exposure to self-stimulation of the medial forebrain bundle. Short-term one-hour stimulation of the medial forebrain bundle for one day after training, which evoked steady self-stimulation behavior, significantly increased the number of c-Fos-positive neurons bilaterally in all of 15 brain structures assayed, as compared to the non-stimulation control. Among them, structures showing a larger number of the stained neurons on the stimulated side were the anterior olfactory nucleus, amygdala, medial caudate-putamen complex, lateral septum, bed nucleus of the stria terminals, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, lateral hypothalamus rostral to the stimulating electrodes, and substantia nigra. Long-term stimulation of the medial forebrain bundle once daily for five successive days, which maintained consistently stable self-stimulation behavior, also increased the number of c-Fos-positive neurons in the aforementioned structures, as compared to the control. However, the long-term rewarding stimulation diminished the increased number of labeled neurons, as compared to the short-term rewarding stimulation. Seven areas, medial caudate-putamen complex, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, rostral lateral hypothalamus and substantia nigra, showed asymmetrical, ipsilateral predominance after the short- and long-term stimulation. However, the stained neuron count in those areas after the long-term stimulation was reduced to less than 50% of that found after the short-term stimulation with the exception of lateral preoptic area and rostral lateral hypothalamus. The results suggest that the development of desensitization of c-Fos response may differ among the reward-relevant brain regions as a consequence of repeated self-stimulation. They also indicate that a larger portion of neurons in the lateral preoptic area and rostral lateral hypothalamus may be implicated in both short- and long-term self-stimulations of the medial forebrain bundle.

Animals

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The lower brainstem.

The origins of projections within the medial forebrain bundle from the lower brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in at least 15 lower brainstem nuclei following injections of a conjugate or horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Dense labeling was observed in the following cell groups (from caudal to rostral): A1 (above the lateral reticular nucleus); A2 (mainly within the nucleus of the solitary tract); a distinct group of cell trailing ventrolaterally from the medial longitudinal fasciculus at the level of the rostral pole of the inferior olive; raphe magnus; nucleus incertus; dorsolateral tegmental nucleus (of Castaldi); locus coeruleus; nucleus subcoeruleus; caudal part of the dorsal (lateral) parabrachial nucleus; and raphe pontis. Distinct but light labeling was seen in raphe pallidus and obscurus, nucleus prepositus hypoglossi, nucleus gigantocellularis pars ventralis, and the ventral (medial) parabrachial nucleus. Sparse labeling was observed throughout the medullary and caudal pontine reticular formation. Several lower brainstem nuclei were found to send strong projections along the medial forebrain bundle to very anterior levels of the forebrain. They were: A1, A2, raphe magnus (rostral part), nucleus incertus, dorsolateral tegmental nucleus, raphe pontis and locus coeruleus. With the exception of the locus coeruleus, attention has only recently been directed to the ascending projections of most of the nuclei mentioned above. Evidence was reviewed indicating that fibers from lower brainstem nuclei with ascending medial forebrain bundle projections distribute to widespread regions of the forebrain. It is concluded from the present findings that several medullary cell groups are capable of exerting a direct effect on the forebrain and that the medial forebrain bundle is the major ascending link between the lower brainstem and the forebrain.

Afferent Pathways

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The upper brainstem.

The origins of projections within the medial forebrain bundle from the upper brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in approximately 15 upper brainstem nuclei following injections of a conjugate of horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Labeled nuclei included (from caudal to rostral): dorsal and ventral parabrachial nuclei; Kolliker-Fuse nucleus; dorsolateral tegmental nucleus; A7 (lateral pontine tegmentum medial to lateral lemniscus); median and dorsal raphe nuclei; distinct group of cells oriented mediolaterally in the dorsal pontine tegmentum below the central gray; B9 (ventral midbrain tegmentum dorsal to medial lemniscus); retrorubral nucleus; nucleus of Darkschewitsch, interfascicular nucleus; rostral and caudal linear nuclei; ventral tegmental area; medial part of substantia nigra, pars compacta; and the supramammillary nucleus. With the exception of the ventral parabrachial nucleus, Kolliker-Fuse, A7, B9 and substantia nigra, pars compacta, each of the nuclei mentioned above sent strong projections along the medial forebrain bundle to the rostral forebrain. Sparse labeling was observed throughout the pontine and midbrain reticular formation. With the exception of the dorsal raphe nucleus, projections to the most anterior regions of the medial forebrain bundle (level of the anterior commissure) essentially only arose from presumed dopamine-containing nuclei-retrorubral nucleus (A8 area), interfascicular nucleus, rostral and caudal linear nuclei, substantia nigra pars compacta, and ventral tegmental area. Evidence was reviewed indicating that major forebrain sites of termination for these dopaminergic nuclei are structures that have been collectively referred to as the 'ventral striatum'. It is concluded from the present findings that several pontine and mesencephalic cell groups are in a position to exert a strong, direct effect on structures in the anterior forebrain and that the medial forebrain bundle is the main communication route between the upper brainstem and the forebrain.

Afferent Pathways

Effects of lesions of various medial forebrain bundle components on lateral hypothalamic self-stimulation.

Unilateral lesions of various medial forebrain bundle components were assessed for their effects on lateral hypothalamic self-stimulation. Damage of areas containig nigrostriatal dopaminergic or ascending noradrenergic neurons had negligible effects on bar pressing, tail moving and alley running for hypothalamic stimulation. Lesions which appeared to destroy most or all of the catecholaminergic fibers in the posterior medial forebrain bundle virtually eliminated reinforced bar pressing and tail moving, but only partially suppressed alley running. The results suggest that brain stimulation reinforcement of the bar press and tail movement tasks depends upon the integrity of neural tissue in the area of the catecholaminergic pathways of the medial forebrain bundle, but not upon specific dopaminergic or noradrenergic systems. The data further suggest that the reinforcement of alley running is at least partially mediated by different neural tissue (possibly non-catecholaminergic) at the level of the posterior medial forebrain bundle lesions.

Animals

Differences in sensitivity to neuroleptic blockade: medial forebrain bundle versus frontal cortex self-stimulation.

The effects of systemic injections of the dopamine receptor antagonist, cis-flupenthixol were tested on intracranial self-stimulation at electrode sites in the medial forebrain bundle and the medial prefrontal cortex. Changes in the reward effectiveness of the brain stimulation were assessed using a curve-shift paradigm. Low to moderate doses of cis-flupenthixol (0.05, 0.1 and 0.15 mg/kg) consistently produced larger upward shifts in the rate-frequency function for medial forebrain bundle than for medial prefrontal self-stimulation. At the highest doses of cis-flupenthixol (0.15 and 0.2 mg/kg), some of the medial forebrain bundle rats failed to respond, whereas all medial prefrontal rats responded at these doses. These results demonstrate that medial forebrain bundle self-stimulation is much more dependent on dopamine systems than is prefrontal cortex self-stimulation.

Animals

Different roles of catecholaminergic and serotoninergic neurons of the medial forebrain bundle on male rat sexual behavior.

The medial forebrain bundle (MFB) plays an important role in the central elaboration of male sexual behavior. However the role of its ascending monoaminergic systems is not well understood. By selective lesions of catecholaminergic and serotoninergic axons of the MFB, produced with 6-OHDA and 5-7-DHT respectively, its possible involvement in male sexual behavior was studied. The evaluation of the behavioral patterns was studied by means of a microcomputer which also permitted the quantification of sequences in the sexual behavior patterns. Lesions with 5-7 DHT increased the intromission-ejaculation sequences and the percentage of ejaculatory males, without modifying other behavioral tests. Lesions with 6-OHDA diminished the number of "active" sexual patterns and motor activity. In order to check the specificity of the chemical lesions, the in vitro uptake of labeled norepinephrine and serotonin was measured, 5-7 DHT lesioned rats show a reduction in the uptake of 5-HT-C14 in the MPOA while 6-OHDA group show a reduction of NA-H3 in the striatum.

Animals

Neural connexions between the medial forebrain bundle, the preoptic area and the basal hypothalamus in the rat: an electrophysiological study.

1. Electrophysiological experiments have been performed on intact cycling female rats to investigate the neural connexions that exist between the medial forebrain bundle, the anterior hypothalamic region, which included the preoptic area, and the basal hypothalamus. Recordings have been made from a total of 351 neurones in the anterior hypothalamus of which 216 were responsive to stimulation of either or both the medial forebrain bundle and basal hypothalamus (arcuate and ventromedial nuclei).2. Forty-six of these cells were responsive to a stimulus applied both to the medial forebrain bundle and the basal hypothalamus with a variety of response combinations. The majority of neurones were orthodromically activated by stimulation in both sites. Inhibition by stimulation of the medial forebrain bundle coupled with orthodromic excitation from the basal hypothalamus, or the reverse situation, was also encountered frequently.3. A few cells were antidromically invaded by the stimulation of the medial forebrain bundle and these received orthodromic or inhibitory inputs from the basal hypothalamus, although one unit outside the anterior hypothalamus was antidromically activated by both stimuli.4. Ninety per cent of all the doubly responsive units that could be antidromically activated by stimulation of the basal hypothalamus received an orthodromic input from the medial forebrain bundle, and no cells in the anterior hypothalamus that projected to the basal hypothalamus were found to receive an inhibitory input from the medial forebrain bundle.5. These results provide electrophysiological evidence for inhibitory and excitatory inputs from the medial forebrain bundle to the preoptic and anterior hypothalamic cells that either project to, or receive connexions from, the basal hypothalamus. Neurones in the preoptic area which project to the basal hypothalamus are implicated in the control of anterior pituitary function, particularly gonadotrophin secretion. These experiments, coupled with functional studies, suggest that there is an excitatory input from the medial forebrain bundle to these preoptic and anterior hypothalamic cells which may modulate adenohypophyseal secretions.

Animals

Differential effects of medial forebrain bundle lesions on adrenocortical responses following limbic stimulation.

Adult male rats had electrolytic lesions placed bilaterally in the medial forebrain bundle and were subsequently implanted with stimulating electrodes in one of the following limbic regions: (1) dorsal hippocampus; (2) ventral hippocampus; (3) medial septal nucleus; (4) basolateral amygdala; (5) mesencephalic reticular formation. Following electrical stimulation, blood was drawn by acute venesection, under either, for plasma corticosterone determinations. In non-lesioned animals, electrical stimulation in all of the limbic regions led to elevated plasma corticosterone levels. In rats with lesions in the medial forebrain bundles, the adrenocortical response to stimulation in the dorsal hippocampus, the basolateral amygdala or the reticular formation was markedly attenuated. On the contrary, the same lesions were without effect upon the corticosterone secretory response to medial septal stimulation, and had only a slight inhibitory effect upon the response to electrical stimulation in the ventral hippocampus. The results demonstrate that the medial forebrain bundle plays a major role in the transmission of impulses to the mediobasal hypothalamus, originating in the dorsal hippocampus, basolateral amygdala or mesencephalic reticular formation, which activate adrenocortical secretion; its role in the transmission of cues arising in the ventral hippocampus or medial septum is, however, minor.

Adrenal Cortex

Light and electron microscopic studies on the medial forebrain bundle in the rat. ii. nerve terminals from the medial hypothalamus.

After the surgical interruption of connections between the medial and lateral hypothalamus of the rat axonal (transient) and nerve terminal degeneration was shown in the medial forebrain bundle (MFB) with light and electron microscopy. Following 1 mm long parasagittal cuts at various rostro-caudal levels the degeneration pattern within the MFB indicated a certain territoral arrangement of terminating fibres from the medial hypothalamus. After a parasagittal cut through the lateral retrochiasmatic area, degeneration was observed in the full length of the MFB. This suggests that a number of axons connect the medial and lateral hypothalamus through this area. With the aid of a parasagittal cut separating totally the medial and lateral hypothalamus, the degeneration of dendrites in the middle portion of the lateral hypothalamus was also revealed. These proved to derive from cells of the ventromedial nucleus.

Animals

Growth of medial forebrain bundle axons into peripheral nerve grafts in the rat.

In rats, we intercepted medial forebrain bundle axons just lateral to the hypothalamus with peripheral nerve grafts which terminated extracranially. The neurons which grew into the nerve grafts were labeled with retrogradely transported fluorescent dyes. Catecholamines were labeled with glyoxylic acid histofluorescence. Most nuclei, particularly the raphe complex and locus coeruleus, which project rostrally into the medial forebrain bundle were labeled. Many catecholamine fibers were observed in the graft even after removal of the superior cervical ganglions. Thus, monoaminergic neurons which were located relatively remotely from the implant site exhibited rather selective regrowth into the nerve grafts.

Animals

Burst stimulation of the medial forebrain bundle selectively increase Fos-like immunoreactivity in the limbic forebrain of the rat.

The present study was designed to evaluate the postsynaptic functional consequences of different presynaptic activity patterns in midbrain dopamine systems using electrical stimulation of the rat medial forebrain bundle and subsequent determination of c-fos expression, used as a marker for neuronal activation, in dopamine target areas, by means of Fos immunohistochemistry. Nerve terminal dopamine release evoked by electrical stimulation of the medial forebrain bundle was monitored in the same animals using in vivo voltammetry. A 5 Hz stimulation consisting of 60 trains of five pulses and lasting 1 min was applied to the medial forebrain bundle. This stimulation was repeated 15 times every 3 min. Its pattern was defined by the interpulse interval which was either 70 ms or 200 ms for burst or regularly spaced stimulation, respectively. Our results show that burst stimulation of the medial forebrain bundle, which increase release of dopamine in target areas, increases the basal Fos-like immunoreactivity in the stimulated hemisphere, while regular stimulation does not affect expression of this protein. Moreover, the increase in Fos-like immunoreactivity induced by burst stimulation is restricted to limbic related structures, i.e. nucleus accumbens shell and intermediate aspect of the lateral septum, and the major island of Calleja, but is not observed in motor related structures (nucleus accumbens core and striatum). Pretreatment with the D1 dopamine receptor antagonist, SCH23390 (0.1 mg/kg, i.p.), blocked the increase in Fos-like immunoreactivity induced by burst stimulation of the medial forebrain bundle, suggesting a role for these receptors in the observed effects. Pretreatment with the 5-hydroxytryptamine2A/2C receptor antagonist ritanserin (0.4 mg/kg, i.p.) did not affect the increase in Fos-like immunoreactivity induced by burst stimulation in the nucleus accumbens shell or in the lateral septum, although it blocked the stimulated enhancement of Fos-like immunoreactivity in the major island of Calleja. The present data indicate that, rather than the absolute mean discharge rate of midbrain dopamine neurons, the temporal organization of the action potentials they generate conveys information to their target areas.

Animals

Cocaine: acute effects on reinforcement thresholds for self-stimulation behavior to the medial forebrain bundle.

Reinforcing thresholds for self-stimulation behavior to the medial forebrain bundle were determined in rats by means of rate-free psychophysical method. The acute administration of cocaine lowered the reinforcing thresholds independent of motor stimulatory effects. These results indicate that cocaine affects the sensitivity of the reward pathways in the brain, and further demonstrate the utility of rate-independent methods in the assessment of drug effects on self-stimulation behavior.

Animals

Suppression of the late component of the carotid occlusion reflex by lesion of the medial forebrain bundle in the rat.

1. The pressor response to a prolonged carotid occlusion in the rat has two components: an early, fast increase in blood pressure, and a late, slow and sustained hypertension. Since the second component can be blocked by a disconnecting lesion near the medial side of the medial forebrain bundle, the hypothesis that this complex structure is involved in the integration of the late pressor reflex was tested. 2. The medial forebrain bundle was partially or completely destroyed, or a disconnecting lesion was made to interrupt some of its medially running afferents and/or efferents. Incomplete lesion caused a transient suppression of the second component in 4 rats, whereas complete lesion in 5 rats or probable interruption of the medial efferent pathways in 3 rats led to suppression of the late component when the one-minute occlusion was performed within one hour after the lesion. 3. The data show that the medial forebrain bundle plays an important role in the integration of the late component of the pressor response to prolonged carotid occlusion.

Animals