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The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys.

The organization of interconnections between the mediodorsal nucleus of the thalamus (MD) and the orbital and medial prefrontal cortex and the agranular insular cortex in the monkey was studied by retrograde and anterograde tracing techniques. In addition to the magnocellular and parvicellular divisions of MD, three other subdivisions can be recognized on the basis of myeloarchitecture, cytoarchitecture, and connections. The first two of these represent a parcellation of the magnocellular division into a lateral, fiber-rich MD pars fibrosa and a medial, poorly myelinated MD pars paramediana adjacent to the midline. The third is a small, poorly myelinated area located at the caudomedial and dorsal edges of MD; it is referred to as MD pars caudodorsalis. MD pars fibrosa is reciprocally interconnected primarily with areas 11, 12 and 13 in the central and lateral part of the orbital cortex. There is a general organization within this projection, with the rostrocaudal axis of the cortex represented from dorsal to ventral in the pars fibrosa, and the mediolateral cortical axis represented from medial to lateral. Cells that project to area 12 also extend laterally into the adjacent pars parvicellularis. MD pars paramediana is more heavily interconnected with the caudal and medial portions of the orbital region, particularly the agranular insular areas and the caudal parts of areas 13 and 14. Cells that project to two caudal areas, 13a and Iad, do not fit with the general organization, in that they are located in the dorsomedial parts of the pars fibrosa and pars paramediana, where they overlap with cells that project to area 14. The pars fibrosa and pars paramediana receive inputs from areas of the ventral forebrain such as the amygdala, piriform (olfactory) cortex, and entorhinal cortex, which project directly to the orbital and agranular insular cortex, as well as from the ventral pallidum. MD pars caudodorsalis is reciprocally interconnected with areas 14, 24, and 32 on the medial surface of the prefrontal cortex. In this part of the nucleus the dorsoventral axis of the medial prefrontal cortex is represented from caudal to rostral in the thalamus. The amygdala and other ventral forebrain structures do not send fibers into the pars caudodorsalis, even though some of these structures project directly to the medial prefrontal cortex. Ventral to MD, and separated from it by the internal medullary lamina, a small region was recognized that appears to be comparable to the anteroventral part of the submedial nucleus previously defined in the rat and cat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Medial temporal lobe activation during encoding and retrieval of novel face-name pairs.

The human medial temporal lobe (MTL) is known to be involved in declarative memory, yet the exact contributions of the various MTL structures are not well understood. In particular, the data as to whether the hippocampal region is preferentially involved in the encoding and/or retrieval of associative memory have not allowed for a consensus concerning its specific role. To investigate the role of the hippocampal region and the nearby MTL cortical areas in encoding and retrieval of associative versus non-associative memories, we used functional magnetic resonance imaging (fMRI) to measure brain activity during learning and later recognition testing of novel face-name pairs. We show that there is greater activity for successful encoding of associative information than for non-associative information in the right hippocampal region, as well as in the left amygdala and right parahippocampal cortex. Activity for retrieval of associative information was greater than for non-associative information in the right hippocampal region also, as well as in the left perirhinal cortex, right entorhinal cortex, and right parahippocampal cortex. The implications of these data for a clear functional distinction between the hippocampal region and the MTL cortical structures are discussed.

Adult↗

Expression of c-fos mRNA following seizures evoked from an epileptogenic site in the deep prepiriform cortex: regional distribution in brain as shown by in situ hybridization.

Using in situ hybridization histochemistry for the detection of c-fos mRNA, we examined the pathways activated by seizures evoked by a focal application of bicuculline into a highly discrete epileptogenic site in the deep prepiriform cortex, the area tempestas (AT). Thirty minutes after the initiation of limbic motor seizures evoked by bicuculline in AT, a marked increase in c-fos mRNA was detected in the hippocampal formation, amygdala, olfactory bulb, piriform cortex, and entorhinal cortex. The increase of c-fos mRNA was strictly dependent upon the infusion of the drug in AT. Infusions of bicuculline in the same dose outside the AT did not increase c-fos mRNA levels. The extent to which the mapping pattern of c-fos mRNA expression was specific to limbic seizures was evaluated by examining another focally evoked seizure model involving the application of bicuculline bilaterally into the inferior colliculus. The absence of any detectable c-fos induction in the limbic system after explosive running-bouncing clonic seizures evoked by bicuculline injected into the inferior colliculus indicates that the pattern of activation that we found in the AT-evoked seizure model is not common to all forms of convulsive activity. Furthermore these observations suggest that the pattern of activation we have observed is seizure dependent and not stress induced. Our results indicate that c-fos mRNA expression is useful in the functional mapping of pathways involved in seizure propagation and that the anatomic pattern of activation is selectively related to the type of seizure evoked.

Animals↗

Cholinergic sprouting is blocked by repeated induction of electroconvulsive seizures, a manipulation that induces a persistent reactive state in astrocytes.

Previous studies have demonstrated that some of the molecular and morphological changes that are characteristic of reactive astrocytes are induced following seizures. This discovery provides the means to experimentally modify the time course and extent of reactive changes in astrocytes following injury and so explore how these reactive changes modulate other events in the injured nervous system. The present study evaluates whether superinduction of a reactive state in astrocytes alters one form of postlesion synaptic reorganization (the sprouting of cholinergic projections in the dentate gyrus after destruction of the entorhinal cortex). Cholinergic sprouting after entorhinal cortex lesions was evaluated in control mice and in mice that experienced electroconvulsive seizures (ECS) from the day of surgery until 12 days postlesion. Animals were prepared for acetylcholinesterase (AChE) histochemistry at 2, 4, 6, 8, 10, 12, 14, and 30+ days postlesion. Quantitative densitometric analyses revealed that the increase in AChE staining that is indicative of cholinergic sprouting was essentially eliminated in the animals that experienced daily ECS. These results indicate that the induction of electroconvulsive seizures during the postinjury period disrupts at least one form of postlesion synaptic reorganization that would otherwise occur. This disruption of synaptic reorganization may be a consequence of the induction of a persistent reactive state in astrocytes.

Acetylcholinesterase↗

The distribution of the projection from the parataenial nucleus of the thalamus to the nucleus accumbens in the rat: an autoradiographic study.

In this study the intrastriatal distribution of afferents arising from the parataenial nucleus of the thalamus was investigated. Tritiated leucine and proline injected into the parataenial nucleus was found to densely label the entire anterior-posterior extent of the medial nucleus accumbens. The projection was for the most part limited to this striatal subregion, although some moderate labelling was found along the medial wall of the anterior caudateputamen . The terminal labelling within accumbens was characterized by a distinct patchiness . Other efferent connections of the parataenial nucleus observed in this study include the thalamic reticular nucleus, the basolateral and central nuclei of the amygdala, the septum, the medial frontal cortex, the entorhinal cortex and subiculum. This projection is distributed to the "limbic afferented " sector of striatum, and there is a nearly complete overlap between the parataenial afferents and those coming from hippocampus. The present findings suggest that the parataenial nucleus is an important thalamic link between limbic and striatal processing.

Afferent Pathways↗

5-HT1A receptor expression during memory formation.

RATIONALE: It has been reported that 5-HT(1A) receptors modulate learning and memory and diverse pharmacological and genetic evidence supports this notion. Nevertheless, there are few works about expression of these receptors during memory formation. OBJECTIVE: We aimed to determine 5-HT(1A) receptor expression in brain areas of untrained, passive, and autoshaping trained groups of rats. METHODS: Ex vivo receptor autoradiography using the ligand agonist [(3)H]8-hydroxy-2-[di-n-propylamino]tetralin] (8-OH-DPAT) was used. RESULTS: The trained group relative to untrained animals showed increases of 5-HT(1A) receptor expression in 14 brain areas, decrements in 7, and no changes in 12. Thus, in contrast to untrained rats, 5-HT(1A) receptor expression of autoshaping trained rats was augmented in the tubercule olfactory, septal nucleus, nucleus accumbens, caudate putamen, globus pallidus, striate, and parietal (1 and 2), temporal cortex (1 and 3), granular retrosplenial cortex (1), amygdala, and median and dorsal raphe nuclei. In contrast, in the latter group, receptors were decreased in the CA1 area, hypothalamus dorsal, frontal cortex (1 and 3), occipital cortex, cingulate cortex (1 and 2), and cuneiform nucleus. There were significant differences between passive vs trained groups, but not regarding untrained rats, in the lateral olfactory tract, dentate gyrus, CA3 area, ventromedial hypothalamic, lateral hypothalamus, preoptic medial, frontal cortex (2), granular retrosplenial cortex (2), entorhinal cortex (1 and 2), piriform cortex, and substantia nigra. CONCLUSIONS: These data suggest that upregulated, downregulated, and "silence" of 5-HT(1A) receptors in brain areas form part of neural circuits engaged in memory formation by demonstrating a high degree of specificity and memory mapping.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cognitive and neuroanatomical effects of triethyltin in developing rats: role of age of exposure.

Long-Evans rat pups were injected i.p. on postnatal day 5 (PND5) or 12 with 0, 3, or 5 mg/kg triethyltin sulfate (TET) and then tested on T-maze delayed alternation on PND21 or 28. Delayed alternation learning was impaired on PND21 and 28 in pups given 5 mg/kg TET. Pups given 5 mg/kg TET on PND5 were more impaired on delayed alternation than pups given 5 mg/kg TET on PND12. Pups given 3 mg/kg TET on PND5 or 12 were unimpaired at either age of testing. On the day following training, pups were sacrificed for histological assessment employing Nissl- or immunohistochemical staining for glial fibrillary acidic protein (GFAP), a putative marker of gliosis. Pups given 5 mg/kg TET on PND5 showed increases in GFAP immunoreactivity (IR) in subiculum, amygdala, hippocampus, piriform cortex, and entorhinal cortex with concomitant decreases in Nissl-stained cells in these regions. Pups given 5 mg/kg TET on PND12 showed increases in GFAP IR in piriform cortex, amygdala and dorsal hippocampus with concomitant decreases in Nissl-stained cells in these regions. Exposure to 3 mg/kg TET on PND5 and PND12 produced a mild increase in GFAP IR in piriform cortex and amygdala but no discernible loss of Nissl-staining in these respective regions. TET-induced behavioral deficits appear related to damage of structural correlates of the human temporal lobe and not piriform cortical pathology. These results demonstrate that the day of exposure greatly influences the magnitude of the cognitive deficits and neuropathology associated with exposure to TET. There appears to be a critical period during postnatal development for the developmental neurotoxicity of this compound.

Animals↗

Transient reduction in hippocampal serotonergic innervation after neonatal parachloroamphetamine treatment.

This study examined the effects of parachloroamphetamine on neonatal forebrain serotonergic (5-HT) innervation. Rat pups were treated with PCA on P3 and P4. Significant reductions in 5-HT content were observed in the hippocampal formation, frontal cortex and entorhinal cortex on P5 and P7. By P14, neocortical 5-HT had returned to normal levels while hippocampal 5-HT values remained less than control. Hippocampal 5-HT content reached normal range by P21. High affinity 5-HT uptake in hippocampal synaptosomal preparations was similarly reduced on P5 and P7 suggesting that 5-HT terminals were being lesioned by PCA. 5-HT uptake recovered significantly by P14 perhaps reflecting the extraordinary plasticity of the 5-HT projections in the neonate. However, in contrast to the complete restoration of hippocampal 5-HT content, 5-HT uptake values remained significantly less than control. No change in 5-HT content was observed in either the hypothalamus or midbrain raphe at any age studied. Thus, the rapid onset of effects, regional selectivity and transient reduction of 5-HT levels recommend the use of PCA in studies of the role of 5-HT in hippocampal development.

Aging↗

In situ hybridization study of interleukin-1 beta mRNA induced by kainic acid in the rat brain.

The distribution patterns of interleukin-1 beta (IL-1 beta) mRNA in various brain regions of saline- and kainic acid-treated rats were examined using in situ hybridization technique. In normal rat brain, the signals of IL-1 beta mRNA were observed in the cerebellar Purkinje cells and in dispersed cells in the hypothalamus. In the case of the kainic acid treatment, IL-1 beta mRNA was intensely induced in the olfactory bulb, lateral septum, thalamus, hypothalamus, polymorphic layers of hippocampus, piriform cortex, amygdala, entorhinal cortex and cerebral cortex at 2 h after the injection of kainic acid. In the hypothalamic region, we observed the induction of IL-1 beta mRNA around the paraventricular hypothalamic nucleus, anterior hypothalamic area, dorsomedial and ventromedial hypothalamic nucleus, mammillary regions and arcuate nucleus. The signal of IL-1 beta mRNA was still expressed 4 h after treatment with kainic acid, less intensely than at 2 h, but above the control level. In these regions, IL-1 beta mRNA was expressed mainly in the glial cells, which were densely stained by Cresyl violet and did not contain glial fibrillary acidic protein. These results suggest that IL-1 beta is produced by a certain type of glial cells, maybe microglia, and might have regulatory functions in the central nervous system.

Animals↗

D-2 dopamine-receptors regulate the release of [3H]dopamine in rat cortical regions showing dopamine immunoreactive fibers.

Using an antibody raised against dopamine the occurrence of dopamine-containing fibers was demonstrated in the prefrontal cortex, anterior cingulate cortex, parietal neocortex, piriform cortex and entorhinal cortex. In extracts of these cortical regions significant amounts of dopamine, although approximately a 100-fold less than in the neostriatum or nucleus accumbens, were detected with high performance liquid chromatography. The release of [3H]dopamine from slices of all these cortical regions was studied in vitro in a superfusion system and desipramine was used to prevent the uptake of [3H]dopamine in noradrenergic nerve terminals. It appeared that the electrically evoked release of radioactivity was inhibited by drugs stimulating D-2 dopamine-receptors in all the regions studied. Cation-exchange column chromatography revealed that the radioactivity released consisted predominantly of [3H]dopamine, indicating that D-2 receptors mediate the inhibition of the release of [3H]dopamine from dopaminergic nerve terminals. Likewise, in the neostriatum as well as in the nucleus accumbens D-2 receptor stimulation inhibits the release of [3H]dopamine. Therefore it is our conclusion that D-2 receptors regulate the release of dopamine from dopaminergic neurons originating in the ventral tegmental area as well as in the substantia nigra.

Animals↗

Adenosine deaminase-containing neurons in the olfactory system of the rat during development.

The development, distribution and olfactory bulb projections of neurons immunoreactive for the enzyme adenosine deaminase (ADA) were studied in olfactory systems of embryonic, early postnatal and young adult rats. On embryonic day (E) 12, ADA-immunoreactivity first appeared in the placode of the olfactory epithelium. On E15, ADA-immunoreactive olfactory receptor and precursor cells gave rise to immunostained axons projecting to the olfactory bulb. Numerous immunostained glomeruli were observed on postnatal day (P) 1. After P25, immunoreactivity within receptor cells and glomeruli decreased. In prenatal and early postnatal animals, ADA-immunoreactive neurons were observed in the anterior olfactory nucleus (AON), dorsal transition area, ventral taenia tecta, primary olfactory cortex (POC), entorhinal cortex and ventral agranular insular cortex. After P25 to P30, these neurons lost their immunoreactivity, except those in the medial AON where light immunostaining persisted. In contrast, ADA-immunostaining of neurons in the horizontal limb of the diagonal band (HDB) and olfactory tubercle increased throughout development. About 70 to 75% of the ADA-immunoreactive neurons in the AON, a small number of those in the POC and about 75% of the ADA-immunoreactive non-cholinergic neurons in the HDB were found to project to the olfactory bulb. The functions of ADA in the olfactory system may be related to the precocious development of, and/or purinergic neurotransmission within, this system.

Adenosine Deaminase↗

Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain.

BACKGROUND: The antidepressant-like effects of brain-derived neurotrophic factor (BDNF) infusions in brain, and the upregulation of BDNF mRNA and its receptor in rats exposed to electroconvulsive seizure (ECS) and antidepressants, suggested a role for increased BDNF protein. METHODS: We measured BDNF protein levels with a two-site enzyme-linked immunosorbent assay (ELISA) in six brain regions of adult male rats that received daily ECS or daily injections of antidepressant drugs. RESULTS: The BDNF ELISA method was validated by the 50% loss of BDNF protein in the brains of +/- BDNF knockout mice, the 60%-100% recovery of spiked recombinant BDNF, and by the amounts and regional variations of BDNF measured in the six brain regions. Ten consecutive daily exposures to ECS increased BDNF protein in the parietal cortex (219%), entorhinal cortex (153%), hippocampus (132%), frontal cortex (94%), neostriatum (67%), and septum (29%). BDNF increased gradually in the hippocampus and frontal cortex, with a peak response by the fourth day of ECS. Increases peaked at 15 hours after the last ECS and lasted at least 3 days thereafter. Two weeks of daily injections with the monoamine (MAO)-A and -B inhibitor tranylcypromine (8-10 mg/kg, IP) increased BDNF by 15% in the frontal cortex, and 3 weeks treatment increased it by 18% in the frontal cortex and by 29% in the neostriatum. Tranylcypromine, fluoxetine, and desmethylimipramine did not elevate BDNF in the hippocampus. CONCLUSIONS: Elevations in BDNF protein in brain are consistent with the greater treatment efficacy of ECS and MAO inhibitors in drug-resistant major depressive disorder and may be predictive for the antidepressant action of the more highly efficacious interventions.

Animals↗

Reduction of neuropeptide Y binding sites in the rat hippocampus after electroconvulsive stimulations.

Repetitive electroconvulsive stimulations (ECSs) increase neuropeptide Y (NPY) synthesis in hippocampal neurons, but whether NPY release and the density of NPY receptors are affected is unknown. In rats exposed to 14 daily ECSs, the concentration of NPY specific binding sites in hippocampal membranes was reduced by about 75% compared with sham, but was unchanged in membranes isolated from the cerebral cortex and the thalamus. In accordance with this, in vitro autoradiography revealed a similar reduction in binding in the dentate gyrus and the CA1 and CA3 regions, but not in the parietal cortex, the entorhinal cortex or the thalamus. These results show significant changes in NPY receptor binding after repeated ECSs, suggesting that NPYergic neurotransmission, most likely within the hippocampus, is strongly affected by ECSs.

Animals↗

Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways.

The present review has provided evidence that very potent ascending brainstem hippocampal synchronizing pathways originate in the rostral pons region (RPO and PPT), and ascend to and synapse with several midline caudal diencephalic nuclei (posterior hypothalamic and supramammillary) which send projections to the medial septal region (MS/vDBB). The medial septal region in turn is a critical nodal point, sending projections to limbic structures such as the hippocampal formation, cingulate cortex, and entorhinal cortex. The pontine and diencephalic nuclei appear to play a critical role in determining the translation of increasing levels of activation into moment to moment changes in the frequency of hippocampal theta field and theta-related cellular discharges, relayed to the MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critical role in translating increasing levels of ascending synchronizing activation into moment to moment changes in the amplitude of hippocampal theta field activity and the accompanying rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role through a balance of activity in the septohippocampal cholinergic and GABA-ergic projections. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-ON cells and the GABA-ergic projections act to reduce the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (theta-OFF cells). Both activities must be present for the generation of hippocampal theta and theta-related cellular activities. The balance between the cholinergic and GABA-ergic projections may determine whether hippocampal synchrony (theta) or asynchrony (LIA, large amplitude irregular activity) occurs. These same ascending pathways influence the electrophysiological and pharmacological properties of the neocortex as well. The functional significance of the ascending brainstem synchronizing pathways is the generalized regulation of activities in these cortical structures as they relate to sensorimotor behavior.

Animals↗

Autoradiographic mapping of brain 5-HT2A binding sites in P and in AA alcohol-preferring rats.

There is considerable evidence for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-HT2A receptor autoradiographic investigation was carried out in two genetically selected rat strains, P and AA alcohol-preferring rats, respectively, as well as in the corresponding NP and ANA alcohol-nonpreferring rats. The aim was to determine if there is any common pattern in 5-HT2A binding site densities that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT2A binding sites, [3H]ketanserin (2 nM) was used. Nonspecific binding was measured in the presence of methysergide 10(-6) M. Results demonstrated a lower level (from 50 to 70%) of 5-HT2A binding sites in the layer IV of prefrontal cortex, frontal cortex, parietal cortex of P rats compared to NP controls. Similarly, in the claustrum, 5-HT2A binding density of P rats was 50% lower than that of NP rats, although this failed to achieve statistical significance. No difference was detected in the other areas investigated, including the olfactory tubercles, nucleus accumbens, caudate putamen, pyriform cortex, ventral tegmental area, temporal cortex, and entorhinal cortex. In AA rats, [3H]ketanserin binding density measured in these brain areas was very similar to that observed in ANA nonpreferring controls, and statistical analysis did not reveal any significant difference between the two rat lines. The present study confirms previous reports demonstrating lower densities of 5-HT2A binding sites in the P rats and provides the first autoradiographic evidence showing that such an alteration does not occur in AA rats. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a shared neurochemical alteration of the 5-HT2A receptor system.

Alcoholism↗

Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain.

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.

3,4-Dihydroxyphenylacetic Acid↗

Ischemic brain damage in rats following cardiac arrest using a long-term recovery model.

A model is described in which transient complete cerebral ischemia is induced in rats by intracardiac injection of potassium chloride. The animals were intubated and mechanically ventilated with a nitrous oxide/oxygen (70:30) mixture. Cardiac arrest was achieved following a brief period of ventricular fibrillation. After 5-6 min, the circulation was restored by cardiopulmonary resuscitation and partial exchange transfusion. Local CBF (LCBF) during ischemia and cardiac resuscitation was studied by injection of [14C]iodoantipyrine into the right auricle at various periods during cardiac arrest, and was subsequently analyzed by autoradiography. No radioactive tracer could be visualized in any brain structure, demonstrating the absence of CBF during the cardiac standstill. LCBF was also studied at 5 min and 6.5 h after cardiac resuscitation. Five minutes of recirculation showed an increase in blood flow in all brain structures studied, ranging between 130 and 400% of control values. After 6.5 h of recirculation, the CBF was decreased in 13 of 24 brain structures by 20-50%, concomitantly with the depressed rate of glucose utilization found in 15 brain structures. The neocortical, hippocampal, and striatal concentrations of labile phosphates, lactate, pyruvate, phosphocreatine, glucose, and glycogen were measured 5 min after cardiac arrest. Extensive energy failure and elevation of lactate levels were observed and were similar to earlier reported values. One week following recovery from the ischemic insult, the animals were perfusion-fixed with formaldehyde. The brains were embedded in paraffin, subserially sectioned, and stained with cresyl violet/acid fuchsin. Histopathological changes were assessed by light microscopy as the number of acidophilic or pyknotic neurons. Morphological changes were observed in the hilus of the dentate gyrus, the hippocampal CA1 and subicular regions, the dorsal and lateral septum, the olfactory tubercle, the primary olfactory cortex, the entorhinal cortex, the amygdaloid nuclei, and the reticular nucleus of the thalamus. The distribution of the morphological changes suggests a transsynaptic mechanism, causing neuronal necrosis primarily in the limbic brain areas.

Animals↗

Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain.

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus niger > globus pallidus > layers IV-V of the frontal cortex > subiculum > entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.

Adult↗