Fos-like Immunoreactive Neurons Research Articles

Distribution of cortical fibers and Fos immunoreactive neurons in ventrolateral medulla and in nucleus tractus solitarius following the motor cortex stimulation in the rat

The present study demonstrates that the motor cortex (MC) stimulation induces expression of Fos-like immunoreactivity (FLI) in the rostro-caudal parts of ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). The coupling of biotinylated dextran (BD) injections with the MC stimulation also permits to identify cortical labeled fibers in the vicinity of FLI neurons in the VLM. Results suggest that the MC is involved in a direct and an indirect modulation of bulbar cardiovascular nuclei.

Central injection in rats of α-melanocyte-stimulating hormone analog: effects on food intake and brain Fos

Lateral cerebroventricular (LCVT) administration of the α-MSH agonist analog Nle 4DPhe 7α-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that α-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.

Induction of Fos-like immunoreactivity in musk shrews after mating

In many mammalian species the neuroendocrine regulation of male and female reproductive behavior is sexually dimorphic. By contrast, many features of female sexual behavior in the musk shrew ( Suncus murinus) more closely resemble those of males than of females of other species. Female musk shrews require testosterone (T), which is neurally aromatized to estrogen, to induce sexual behavior. Aromatization occurs in the medial preoptic area (MPOA), and this region is critical for the expression of female receptivity. To compare neural responses to sexual behavior in females and males, we compared the number of Fos-like immunoreactive (Fos-ir) neurons after mating in musk shrews. In both males and females the number of Fos-ir neurons was increased by mating activity in the granule layer of the accessory olfactory bulb (gr-AOB), the bed nucleus of the stria terminalis (BNST), MPOA, the medial amygdala (MeA), and the region corresponding to the midbrain central tegmental field (CTF). Although Fos was induced by mating in several regions, this response was only dimorphic in the ventral medial nucleus of the hypothalamus (VMN), where mating significantly increased Fos-ir in females, but not in males. In both sexes, only the gr-AOB displayed an increase in Fos-ir after exposure to chemosensory cues alone. Thus, the pattern of Fos expression in the brain after mating is only sexually dimorphic in one region, the VMN. Further, in spite of past behavioral studies done in this species, which show a role for pheromones in induction of receptivity, these data show that exposure to pheromones does not induce Fos in structures caudal to the olfactory bulbs.

Further Evidence That the Central Nucleus of the Amygdala Is Associated with the Ethanol‐Induced Locomotor Response

The effect of ethanol on the number of Fos-like immunoreactive (Fos-li) neurons was previously studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains (Hitzemann and Hitzemann, Alcohol. Clin. Exp. Res. 21:1497-1507, 1997). The data obtained suggested that the locomotor activation response to ethanol found in the D2 but not the B6 strain was associated with an increase in the number of Fos-li neurons (a putative measure of synaptic activity) in the central nucleus of the amygdala (CeA), but not in other brain regions, including the basal ganglia. The current study was performed to obtain data supporting a role for the CeA in the locomotor response. B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol (1.5 g/kg). The animals from the extreme phenotypes (> 1 SD from the mean) were denoted as very high and very low activity (HH, LL) and differed in their ethanol response by >9,000 cm/15 min (baseline activity was similar in both phenotypes: 5,500 cm/15 min). These extremes especially differed from the parental strains in that the LL group showed a significant ethanol-induced inhibition of activity. After 2 weeks, HH and LL animals were rechallenged with 1.5 g/kg of ethanol or saline and the number of Fos-li neurons determined 1 hr later. In the HH group, ethanol increased the number of Fos-li neurons >600%, whereas in the LL group the increase was 170% (difference: p < 0.001). The increase in the HH group was principally located in the GABA neuron-rich lateral aspect of the CeA and not in the medial posterior-ventral division or the caps division. No significant difference was found between groups in the Fos response for the basolateral or lateral amygdala. Other brain regions were also examined, including the basal ganglia, the hippocampus (CA1, CA3, and dentate gyrus), the bed nucleus of the stria terminalis, and several cortical regions. In some regions (e.g., the bed nucleus), a significant ethanol effect was detected, but it did not differentiate the HH and LL groups. Overall, the data obtained further argue that the CeA has an important role in regulating the acute locomotor response to ethanol.

Infrasonic Stimulation Induced Fos Expression in Medullary Catecholaminergic Neurons in Rats

To clarify the effects of infrasound on the medulla, catecholaminergic neurons in the medulla expressing Fos were investigated in the rats by immunohistochemical method. After exposure to infrasound (8Hz, 120dB) for 2 hours, animals were sacrificed and sections of the medulla were stained immunohistochemically for Fos and tyrosine hydroxylase (TH). Many Fos-like immunoreactive neurons were found in the nucleus tractus solitarii (NTS) and Ventrolateral medulla (VLM) at the middle and caudal levels of medulla, only a few of them scattered in the reticular formation between NTS and VLM. Some Fos immunoreactive neurons were also labeled with TH. These results indicated that medulla was sensitive to infrasonic stimulation and some medullary catecholaminergic neurons might be involved in the responses to the stress produced by infrasound.

Spatial and temporal expression of c-Fos protein in the spinal cord of anesthetized rat induced by subcutaneous bee venom injection

In order to study central neuronal components involved in subcutaneous (s.c.) bee venom-induced persistent pain (a new tonic pain model), we use Fos immunostaining technique to study the spatial and temporal patterns of neuronal activity in the spinal cord of anesthetized rats. Following intraplantar bee venom injection, Fos-like immunoreactive (ir) neurons were only seen from L 1 to S 3 rostrocaudally with distinct distribution at L 4–5 segments. At segments of L 1–2 and S 1–3, Fos-ir labelings were diffusely and symmetrically distributed on both sides of the gray matter; however, at L 4–5 segments, Fos-ir neurons were densely localized in medial portion of laminae I–II, less densely in laminae V–VI and a few in laminae VII and X ipsilateral to the injection side. No Fos labeling was seen in ventral horn of the spinal cord at L 4–5 segments. Fos protein began to express only within lamina I at 0.5 h, but increased over the whole dorsal horn at 1 h and reached peak labeling at 2 h after bee venom. Expression of c-Fos in laminae I–II decreased at 4 h, and completely disappeared at 24 h, however, labeling in laminae V–VI disappeared much slowly and existed even at 96 h after bee venom. Within laminae III–IV, Fos-ir neurons could not be seen at 0.5 h, but began to be seen at 1 h and appeared to exist even at 24 h after bee venom. Systemic morphine suppressed c-Fos expression dose-dependently in both superficial and deep layers of dorsal horn and the latter region was much more sensitive to morphine than the former one. The present results demonstrated that prolonged neuronal activities in superficial and deep layers of dorsal horn were essential to mediation of bee venom induced tonic pain and may have different roles in generation and/or modulation of spontaneous pain and hyperalgesia and allodynia.

Phenotypic Characterization of Neuroleptic-Sensitive Neurons in the Forebrain: Contrasting Targets of Haloperidol and Clozapine

The prototypical neuroleptic haloperidol and the atypical antipsychotic clozapine induce distinctly different patterns of c-fos expression in the forebrain. While haloperidol appears to increase c-fos expression via its D2 dopamine receptor antagonist properties, the receptor mechanisms by which clozapine produces its unique pattern of c-fos expression are not known. The present experiments sought to address this question by determining the phenotypes of neurons in which clozapine increases Fos-like immunoreactivity (FLI). Fos immunostaining combined with in situ hybridization histochemistry using a cDNA oligonucleotide probe for D3 receptor mRNA indicated that the great majority (95%) of clozapine-induced FLI neurons in the major island of Calleja (ICjM) express D3 receptors. Similarly, in the nucleus accumbens (NAc) and lateral septal nucleus (LSN), the majority of clozapine-induced FLI neurons express D3 receptor mRNA (NAc 69%; LS 73%). In marked contrast, haloperidol-induced FLI neurons failed to express D3 receptors in any brain region. Studies with oligonucleotide probes for enkephalin (ENK) and dynorphin (DYN) indicated that clozapine increases c-fos expression in both ENK and DYN containing neurons in the NAc (ENK 40%, DYN 53%) and LSN (ENK 32%, DYN 59%). Haloperidol also increases c-fos expression in ENK and DYN containing neurons, albeit in a different pattern (striatum: ENK 93%, DYN 20%; nucleus accumbens: ENK 46%, DYN 36%; lateral septum: ENK 29%, DYN 18%). The present results demonstrate that haloperidol and clozapine target different populations of neurons even in regions such as the NAc and LSN, where they both increase c-fos expression. In addition, the fact that the majority of clozapine-sensitive neurons in NAc, LSN, and ICjM express D3 receptors suggests that activity at these receptors may contribute to the unique clinical profile of this antipsychotic agent. These data indicate that D3 receptors may represent novel targets in the pharmacotherapy of schizophrenia.

Genetics, Haloperidol, and the Fos Response in the Basal Ganglia: A Comparison of the C57BL/6J and DBA/2J Inbred Mouse Strains

The haloperidol-induced increase of Fos-like immunoreactive (Fos-li) neurons in the basal ganglia was compared in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The D2 strain is 10-fold more sensitive than the B6 strain to haloperidol-induced catalepsy, a putative animal model of the extrapyramidal symptoms (EPS) seen after the administration of typical neuroleptics. In contrast, the strains are equally sensitive to the haloperidol facilitation of prepulse inhibition of the acoustic startle response, a measure of drug efficacy on the mesolimbic dopamine system. The haloperidol effects on Fos-li neurons were examined over the range of 0.1 to 6.0 mg/kg; the ED50s for haloperidol-induced catalepsy are 0.4 and 3.8 mg/kg in the D2 and B6 strains, respectively. In neither the core or shell of the nucleus accumbens nor the caudate-putamen (including the dorsolateral aspect) did the D2 strain show a greater Fos response compared to the B6 strain. In fact, in the dorsolateral caudate-putamen, the B6 strain showed a modest but significantly greater Fos response. However, at the output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra zona reticulata (SNr), the D2 strain consistently showed a greater Fos response. These data suggest that the EP and SNr may be important to understanding the difference in haloperidol-induced catalepsy between the D2 and B6 strains.

Seizures in rats treated with kainic acid induce Fos-like immunoreactivity in locus coeruleus.

Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in limbic structures, which send efferents to the locus coeruleus (LC). Following KATS, brain stem sections were stained for Fos immunocytochemistry and double immunostained for Fos and dopamine beta-hydroxylase (DBH). KA-treated animals showed significantly greater numbers of FLI neurons in the LC than control animals (p < 0.05). Co-localization of DBH/Fos was observed in 89.7% of the LC neurons in KA-treated animals and in 1.4% of LC neurons in control animals. Thus, KATS heavily induce Fos in DBH-containing neurons in the LC, which are known to project to the hippocampus. However, the role of activation of the LC noradrenergic neurons during KATS is not well understood at this present time.

Induction of Fos-like immunoreactivity in the hypothalamic, medullary and thoracic spinal cord neurons following middle cerebral artery occlusion in rats

This study is a sequel of our previous work which demonstrated the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord motoneurons of rat following permanent occlusion of the middle cerebral artery (MCA). We report here Fos-LI in the hypothalamic, medullary and thoracic spinal cord neurons some of them are believed to be involved in cardiovascular regulation after the cerebral ischaemic insult. At 1 and 2 h, especially in the latter after right sided MCA occlusion, Fos-LI confined to the cell nucleus, was detected bilaterally in cells of the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the hypothalamus, the nucleus of the solitary tract (NTS), the area postrema and ventrolateral medulla (VLM). A few Fos-like immunoreactive neurons were observed in the nucleus raphe pallidus and obscurus, and in the intermediolateral nucleus of the thoracic spinal cord. In the corresponding areas in sham-operated animals, Fos-like immunoreactive neurons were sparsely distributed or absent. Colocalization study showed that a variable number of the Fos-like immunoreactive neurons in NTS and VLM coexpressed tyrosine-hydroxylase (TH) immunoreactivity. Such double labelled neurons appeared to be more common in the latter. It is suggested that the induction of Fos-LI in neurons of the hypothalamus, medulla and thoracic spinal cord was linked to cardiovascular regulation following the middle cerebral artery occlusion.

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat.

Wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) injection into the midbrain periaqueductal gray (PAG) resulted in heavy accumulation of retrogradely labeled neurons in the lateral habenular nucleus (LHb) bilaterally. When the left femoral artery was persistently ligated for 2 h, the expression of Fos-like immunoreactivity (FOS-LI) was also found bilaterally in the LHb. In the present study, by combining the retrograde labeling method of injecting WGA-HRP into the PAG and the immunohistochemical staining of the FOS-LI neurons in the LHb induced by occlusion of the femoral artery, it was demonstrated that there are neurons containing both HRP labeling and FOS-LI. These neurons appeared to be located mainly in the medial part and posterior half of the LHb, and constitute about 24% of the total number of all labeled cells.

Genetics, Ethanol and the Fos Response: A Comparison of the C57BL/6J and DBA/2J Inbred Mouse Strains

The effect of ethanol (0.25 to 4 g/kg) on the number of Fos-like immunoreactive (Fos-li) neurons was studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. The brain regions emphasized in the analysis were from the basal ganglia and some associated limbic nuclei. The question addressed was whether or not the D2 and B6 strains differed in these regions in a way that could explain the marked psychomotor stimulation of the D2, but not the B6, strain over the dose range of 1 to 2 g/kg of ethanol. Over the dose range of 0.25 to 2 g/kg, ethanol caused a modest increase in the number of Fos-li neurons within the caudate putamen (dorsolateral and dorsomedial) and the nucleus accumbens (core and shell), but there were no marked strain effects. There was no significant effect in either strain of ethanol treatment (0.25 to 2 g/kg) in the globus pallidus, ventral pallidum, and subthalamic nucleus. However, at 4 g/kg, there was a dramatic (> 100%) increase of Fos-li neurons in the D2 but not B6 strain. A similar effect was noted in the entopeduncular nucleus, the substantia nigra zona reticulata (and compacta), but not the ventral tegmental area. A marked and substantial (> 200%) Fos response was seen in the central amygdaloid nucleus (CeA) of the D2 strain over the entire dose range; in contrast, a substantial Fos response in the B6 strain was seen only at the 4 g/kg dose. The paraventricular thalamic nucleus, in general, paralleled data in the CeA; but, the Fos response was more modest, and the results for the D2 strain were significant only at the 2 g/kg dose. Overall, data suggest that ethanol at low to moderate doses induces significant, strain-dependent Fos responses in some limbic structures, but not in the basal ganglia. The possibility is considered that activation of some neurons in the CeA are permissive for expression of the ethanol-induced increase in motor activity.

Intradermal 5-HT induces Fos expression in rat dorsal horn neurons not via 5-HT 3 but via 5-HT 2A receptors

We investigated the effects of peripherally administered 5-HT on the secondary neurons in the spinal cord of rats using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. The intradermal administration of 5-HT (30, 60 μg) induced a large number of FLI neurons in the ipsilateral dorsal horn. In animals given 5-HT 2A receptor agonists (DOI: 0.28∼2.8 μmol/kg, α-methyl 5-HT: 0.28∼2.8 μmol/kg) intradermally, immunoreactive neurons were evoked in the same manner as those given 5-HT. Other agonists, including 5-HT 3 receptor agonists ( m-CPG: 16∼32 μmol/kg, 2-methyl 5-HT: 0.0028∼2.8 μmol/kg), did not induce FLI neurons at any dose examined. Furthermore, 5-HT 2A receptor antagonist (ketanserin: 1 mg/kg, i.p.) suppressed the expression of FLI in the dorsal horn caused by peripheral 5-HT, but 5-HT 3 receptor antagonist (tropisetron: 1 mg/kg, i.p.) did not. These findings suggest that the 5-HT-induced nociceptive response is mediated by 5-HT 2A receptors in the periphery.

Localization of Fos-like immunoreactivity induced by the NK3 tachykinin receptor agonist, senktide, in the guinea-pig brain.

1. The effects of intracerebroventricular (i.c.v.) administration of the NK3 tachykinin receptor agonist, senktide (10 nmol each side), in guinea-pigs pretreated with the selective NK3 tachykinin receptor antagonist, SR142801 (3 mg kg(-1) subcutaneous, s.c., 30 min before senktide), or its less active enantiomer, SR142806 (3 mg kg(-1) s.c. 30 min before senktide), on behaviour and on the distribution of Fos-like immunoreactivity (Fos-LI) in central neurones were investigated. Guinea-pigs were chosen for the study since they possess NK3 tachykinin receptors with pharmacological characteristics similar to those in man. 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 tachykinin receptors in wet-dog shake behaviour. 3. Senktide induced increased numbers of Fos-LI neurones in the following brain areas: frontal, parietal and piriform cortex, the lateral septum, the CA1, CA2, subiculum and dentate gyrus of the hippocampus, most areas in the amygdala, thalamus and hypothalamus, medial geniculate nucleus and the ventral cochlear nucleus. Pretreatment with SR142801, but not with SR142806, before administration of senktide inhibited Fos-LI expression in the cingulate cortex, dentate gyrus of the hippocampus, some regions of the thalamus, hypothalamus and amygdala and the ventral cochlear nucleus. 4. The present results are the first demonstration that senktide induces Fos-LI in widespread areas of the guinea-pig brain. It is proposed that NK3 tachykinin receptors may play a more extensive role in the control of diverse brain functions, including cortical processing, learning and memory, neuroendocrine and behavioural regulation, than is currently recognized.

Seizures and proto-oncogene expression of fos in the brain of adult genetically epilepsy-prone rats.

The mechanisms and brain circuitry that render genetically epilepsy-prone rats (GEPRs) susceptible to acoustically induced seizures are not completely known. The present study explores the neuroanatomy of acoustically induced seizures by immunohistochemical analysis of the proto-oncoprotein fos after intense acoustic stimulation (AS) with and without seizures. Acoustic stimulation induced tonic convulsions in GEPR-9s, but not in control rats. Locations of brain nuclei showing fos-like immunoreactive (FLI) neurons following AS with and without seizures were mapped. Semiquantitative methods were used to compare FLI neuron numerical densities in AS control rats and GEPRs. Many brain areas exhibited profound FLI in AS control rats and GEPRs. Unexpectedly, the cochlear nuclei and the central nucleus of the inferior colliculi (ICc), both of which are requisite for AGS initiation, exhibited a diminished fos expression in animals having seizures compared to AS controls. In contrast, GEPRs displayed a significant increase in FLI neurons within the dorsal cortex of the IC (ICd) compared to AS controls. This finding may suggest a seizure-related amplification of the auditory signal between the ICc and the ICd. Other nuclei, known to be involved in auditory transmission (i.e., superior olivary complex; trapezoid nucleus; dorsal nucleus of the lateral lemniscus, DNLL), did not show differential FLI densities between seizure and AS control animals. In contrast, seizure-induced FLI was observed in many nonauditory brain nuclei. Of particular interest was the identification of an intensely labeled nucleus in the GEPR. This nucleus resides in the most posterior and dorsal-lateral part of the pedunculopontine tegmental nucleus-pars compacta (PPTn-pc) immediately adjacent to the DNLL and extends posteriorly into the superior lateral subnucleus of the lateral parabrachial area (SLPBn). Therefore, we have tentatively termed this nucleus the PPSLPBn. The PPSLPBn lies in a region previously described as a mesencephalic locomotor region and a suspected functional involvement of this nucleus in display of seizure activity is under investigation. Other brain stem nuclei showing differential fos expression between GEPRs and AS control rats are also described.

C-fos expression in the trigeminal sensory complex and pontine parabrachial areas following experimental tooth movement.

Ortodontic tooth movement causes continuous pain. However, it does not appear immediately, usually appearing after the application of orthodontic force to the teeth. Mechanically induced inflammatory responses in the periodontal membrane are assumed to be related to the mechanism of the later pain sensation. In the present study, we investigated Fos-like immunoreactivity in the trigeminal sensory complex and pontine parabrachial areas 24 h after the commencement of experimental tooth movement. An orthodontic elastic module was unilaterally inserted between upper molars. Following experimental tooth movement, Fos-like immunoreactive neurons appeared ipsilaterally in the trigeminal subnucleus caudalis and bilaterally in the lateral parabrachial nucleus. These results indicate that experimental tooth movement evokes delayed and continuous nociception after application of orthodontic force to the teeth and that the nociceptive information would be conveyed to the ipsilateral trigeminal subnucleus caudalis and further processed, at least in part, to the lateral parabrachial nucleus.

Expression of Fos-like immunoreactivity in the brain and spinal cord of rats following middle cerebral artery occlusion

This study examined c-fos protein expression in the brain and spinal cord of rats following permanent occlusion of the middle cerebral artery (MCA) above the rhinal fissure. At 1 h after right-sided MCA occlusion, Fos-like immunoreactivity (Fos-LI) was detected in neurons not only in the ipsilateral cerebral cortex but also in the spinal cord. In the latter, Fos-LI was localized in the nucleus and perikarya of neurons in the grey matter, notably the large motor neurons in the ventral horn. Fos-LI was most intense at 2-4 h, but became undetectable after 48 h in the cerebral cortex and 72 h in the spinal cord. In sham-operated animals, Fos-LI was almost undetectable or virtually absent. It was also not detected in the core territory supplied by the MCA at any time points after arterial occlusion. When the ischaemia-induced neuronal damage in both the cerebral cortex and spinal cord was evaluated by Nissl staining, some neurons appeared atrophic. We conclude that the induction of Fos-LI in neurons of the cerebral cortex and spinal cord is linked respectively to early onset-short stimulation and persistent excitatory or disinhibition phenomenon as a result of focal ischaemic brain injury.

Distribution of Fos-Like Immunoreactivity in the Medullary Reticular Formation of the Rat after Gustatory Elicited Ingestion and Rejection Behaviors

The distribution of neurons in the medullary reticular formation (RF) activated by the ingestion of sucrose or rejection of quinine was examined using standard immunohistochemical techniques to detect the expression of the Fos protein product of the immediate-early gene c-fos. Double-labeling techniques were used to gain further insight into the possible functional significance of RF neurons exhibiting Fos-like immunoreactivity (FLI). Compared with sucrose and unstimulated controls, quinine elicited significantly more FLI neurons in three specific RF subdivisions: parvocellular reticular nucleus (PCRt), intermediate reticular nucleus (IRt), and dorsal medullary reticular nucleus (MdD). Moreover, the number of FLI neurons in the RF of quinine-stimulated animals was significantly correlated with the degree of oromotor activity. Thus, the distinct distribution of FLI neurons throughout the RF after quinine may reflect the activation of a specific oral rejection circuit. The double-labeling results indicated a high degree of segregation between FLI neurons and premotor projection neurons to the hypoglossal nucleus (mXII) retrogradely labeled with Fluorogold. Thus, although there were a significant number of double-labeled neurons in the RF, the major concentration of premotor projection neurons to mXII in IRt were medial to the preponderance of FLI neurons in the PCRt. In contrast, there was substantial overlap between FLI neurons in the RF and labeled fibers after injections of the anterograde tracer, biotinylated dextran into the rostral (gustatory) portion of the nucleus of the solitary tract. These results support a medial (premotor)/lateral (sensory) functional topography of the medullary RF.

Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c- fos-like immunoreactivity

Expression of proto-oncogene c- fos was immunohistochemically examined in the central and basolateral amygdaloid nuclei in rats after ingestion of taste solutions (0.5 M sucrose or 0.005 M saccharin), intragastric infusion of these solutions, or an intraperitoneal injection of malaise-inducing lithium chloride (LiCl). c- Fos-like immunoreactive neurons were distributed most densely in the central nucleus in response to the LiCl injection, followed by the ingestion and intragastric infusion of sucrose. The intraoral infusion of sucrose, but not of saccharin, elicited intense c- fos expression in the central nucleus after establishment of conditioned taste aversion to these taste stimuli. The results are discussed in terms of post-ingestional factors and the conditioned illness reaction after taste aversion learning.

Changes in formalin-evoked spinal Fos expression and nociceptive behaviour after oral administration of Bufferin A (aspirin) and L-5409709 (ibuprofen+caffeine+paracetamol)

This study compares the effects of two non-steroidal anti-inflammatory drugs, Bufferin A (BA) and L-5409709 (L-54), on nociceptive behaviour and spinal Fos expression induced by subcutaneous formalin in the rat. BA contains aspirin. L-54 contains ibuprofen, caffeine and paracetamol. Doses based on the human posology were administered orally 30 or 40 min before subcutaneous intraplantar injection of formalin (1.5%, 50 μl) in the right hindpaw. Low doses (BA, 24 mg/kg; L-54, 21.5 mg/kg) did not significantly affect the behavioural pain response. High doses (BA, 480 mg/kg; L-54, 430 mg/kg) reduced the late phase of the response by 42% and 62% respectively, but did not affect the early phase of the response. No sedative side-effects were observed. The two drugs had different effects on the number of spinal Fos-like immunoreactive neurones 2 h after the formalin injection. Fos expression was reduced after BA treatment, and this reduction was correlated to and matched the reduction of the pain response. In contrast, Fos expression after L-54 treatment was not reduced and was not correlated to the reduction in the pain response. The Fos results reveal clear differences in the way that BA (aspirin) and L-54 (ibuprofen+caffeine+paracetamol) affected transmission of the noxious signal. They suggest that BA did not act beyond the spinal cord and that L-54 had more central sites of action than BA.