Differential migration of Th1 and Th2 cells--implications for vaccine and infection studies

We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 microg/kg) and sulfated CCK-8 (3.5 microg/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0. 3-fold respectively). Injections of leptin-CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin-CCK to regulate food intake.     

The temporal course of expression of c-Fos and Fos B within the medial preoptic area and other brain regions of postpartum female rats during prolonged mother–young interactions.

Maternal behavior is associated with an increase in the expression of c-Fos and Fos B within neurons of the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (vBST). Whether this increase wanes as the duration of mother–young interaction increases is unknown. By varying the length of mother–young interactions in postpartum rats, the authors found that within the MPOA/vBST, the levels of both c-Fos and Fos B, once elevated, remained significantly above control levels through 47 hr of pup exposure. The persistence of c-Fos and Fos B within the MPOA/vBST of females that remained with pups was almost unique in that only one other neural area, the anterior magnocellular part of the paraventricular hypothalamic nucleus, showed such a response. Because MPOA/vBST neurons are essential for maternal behavior, the results suggest that c-Fos and Fos B expression within these regions may be necessary to maintain their normal functional activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Injection of corticotropin-releasing hormone into the locus coeruleus or foot shock increases neuronal Fos expression

Previous research suggests that corticotropin-releasing hormone can act in the locus coeruleus to increase the firing of locus coeruleus neurons and elicit physiological responses resembling those associated with stress. The present study used immunocytochemical detection of Fos as a measure of neuronal activation to identify brain areas that were activated by bilateral injections of corticotropin-releasing hormone into the locus coeruleus of rats. Injection of corticotropin-releasing hormone into the locus coeruleus increased the expression of Fos in the locus coeruleus as compared with injection of vehicle into the locus coeruleus or injection of corticotropin-releasing hormone into neighbouring pontine sites. The pattern of Fos expression throughout the brain after injections of corticotropin-releasing hormone into the locus coeruleus was generally consistent with the anatomical organization of efferent projections arising from the locus coeruleus; increased Fos expression was observed in many brain areas including the ventral lateral septum, septohypothalamic nucleus, bed nucleus of the stria terminalis, the central amygdaloid nucleus, the dorsomedial nuclei of the hypothalamus, and the thalamic paraventricular and rhomboid nuclei. Foot shock also increased Fos expression in the locus coeruleus and the other brain regions that expressed Fos after corticotropin-releasing hormone injections into the locus coeruleus. A few brain regions, most notably the hypothalamic paraventricular nucleus, expressed Fos in response to foot shock but not corticotropin-releasing hormone. These results indicate that local injection of corticotropin-releasing hormone into the locus coeruleus stimulates the activity of the locus coeruleus neurons. However, the pattern of Fos expression throughout the brain evoked by injection of corticotropin-releasing hormone into the locus coeruleus does not fully replicate the effects of foot shock.     

Contextual Fear Conditioning Is Associated With Lateralized Expression of the Immediate Early Gene c-fos in the Central and Basolateral Amygdalar Nuclei.

Fos, the protein product of the immediate early gene c-fos, was used to map functional circuitry underlying contextual conditioned fear. Male rats were given footshocks in a distinctive context and later tested using freezing as the behavioral measure and compared with no-shock and no-retention-test control groups. An increased number of Fos-immunoreactive neurons was found in the lateral part of the central nucleus and in the anterior basolateral and lateral amygdalar nuclei in the brains of the conditioned-fear group compared with controls. Further, a greater number of Fos-immunoreactive neurons was observed in the right central and anterior basolateral nuclei compared with the number of labeled neurons in these structures on the left. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

c-Fos expression in brain in response to hypotension and hypertension in conscious rats

Hypotension- and hypertension-evoked expression of the protein product, Fos, of the immediate early gene c-fos was assessed throughout the rat brain as an approach for describing the neuronal populations that respond to alterations in arterial blood pressure. Conscious, chronically catheterized rats were treated with the vasoconstricting drug phenylephrine or the vasodilatating drug hydralazine to increase or decrease, respectively, arterial pressure by approx. 40 mm Hg for 90 min. Rats were then anesthetized, fixed by vascular perfusion, and sections representing the entire brain were processed for the immunocytochemical localization of Fos. In control rats treated with isotonic saline, few Fos-positive neurons were observed. In contrast, phenylephrine and hydralazine treatments resulted in different, yet reproducible, patterns of Fos expression in the brain, with hydralazine evoking Fos expression in more brain regions than phenylephrine. Brain regions containing Fos-positive neurons in rats treated with hydralazine included nucleus tractus solitarius, area postrema, caudal ventrolateral medulla, rostral ventrolateral medulla, bed nucleus of the stria terminalis, amygdala, paraventricular nucleus, supraoptic nucleus, subfornical organ and the Islands of Calleja. The nucleus tractus solitarius, paraventricular nucleus and the amygdala also contained Fos-positive neurons in phenylephrine-treated rats, although the number of Fos-positive neurons was always less than that noted in the hydralazine-treated rats and the location of Fos-positive neurons within these regions tended to differ between treatments. These results generally fit within an emerging understanding of brain circuitry underlying cardiovascular regulation.     

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.     

Neurons in the hypothalamic paraventricular nucleus that project to the rostral ventrolateral medulla are not activated by hypotension

The retrogradely-transported tracer, rhodamine-tagged microspheres was injected into the pressor region of the rostral ventrolateral medulla (RVLM) to enable detection of paraventricular neurons in the hypothalamus that project to the RVLM. The protein, Fos, was detected immunohistochemically and used to highlight neurons that were activated by hypotension (-16+/-5 mmHg) induced by diazoxide (30 mg/kg s.c.). Compared to controls, Fos production was increased by three-fold in the parvocellular paraventricular nucleus but there was no significant increase in the number of retrogradely-labelled cells that expressed Fos. The results suggest paraventricular nucleus (PVN) neurons projecting to the RVLM are not activated by hypotension.     

Hippocampal pyramidal cell disarray correlates negatively to cell number: implications for the pathogenesis of schizophrenia

It has been well documented that the medial parvocellular subnucleus of the hypothalamic paraventricular nucleus (PVN) participates in immune regulation by releasing corticotrophin-releasing hormone (CRH), which triggers the hypothalamus-pituitary-adrenal axis, leading to immunosuppression. Little is known about other possible influences of PVN on immunomodulation. Evidence, however, has been accumulating recently, indicating possible involvement of other subnuclei of this nucleus. By using the c-fos technique, the present study investigated the neuronal groups of the PVN that were activated in response to intracerebroventricularly administered IL-1 beta. In addition to strong Fos expression in the dorsal part of medial parvocellular subnucleus of the PVN, where CRH neurons are located, two more neuronal groups were found to express Fos protein. One of which was the oxytocin-immunoreactive magnocellular neurons, mainly concentrated in the anterior and medial magnocellular subnuclei of the PVN. The magnocellular PVN subnuclei are known to project to, and release their hormones, in the posterior pituitary. Another group of Fos-immunoreactive neurons were found in the brainstem and spinal cord projecting area of the PVN. By combining retrograde tracing technique and Fos immunohistochemistry, it was proved that many of the spinal cord projecting PVN neurons were activated following IL-1 beta administration, through which the spinal cord sympathetic outflow might be regulated. The present study indicates that the hypothalamic PVN may serve as an integrative center for immunomodulation via three channels, i.e., the CRH and oxytocin neuroendocrinological and the PVN-spinal cord sympathetic neural channels.     

A preliminary study of factors associated with psychological adjustment and disease course in school-age children infected with the human immunodeficiency virus

OBJECTIVE: To evaluate the anti-inflammatory/analgesic effects of lornoxicam in the carrageenan model of inflammatory nociception. MATERIAL AND METHODS: Three hours after intraplantar carrageenan (6 mg/150 microl of saline), we assessed the effects of pre-administered lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg i.v., n=10 rats for each group) on both the peripheral oedema and number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar L4-L5 segments, in the awake rat. RESULTS: Lornoxicam dose-relatedly reduced both the carrageenan evoked oedema (r=0.63 and r=0.53 for paw and ankle diameter respectively; p<0.001 for both) and total number of spinal c-Fos-LI neurons (r=0.79; p<0.001), with the strongest effect corresponding to a 75 +/- 2% reduction of the number of c-Fos-LI neurons (p<0.001) for the highest dose (9 mg/kg), and a 45 +/- 3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Reductions of both the peripheral oedema and spinal c-Fos expression were correlated (r=0.74 and r=0.57 for the paw and ankle diameter respectively; p<0.001 for both). CONCLUSIONS: Our results demonstrate that lornoxicam reduces in parallel both the carrageenan-evoked oedema and spinal c-Fos expression, with clear evidence for a potent effect of low doses of lornoxicam. Correlated reductions in c-Fos expression and paw oedema suggest a predominantly peripheral site of action of lornoxicam.     

Endogenous expression of C-Fos in hypothalamic nuclei of neonatal rabbits coincides with their circadian pattern of suckling-associated arousal

Rabbits exhibit an unusually restricted form of maternal care. The newborn young are only nursed for about 3 min every 24 h and drink up to one third of their body weight in this time. They show a circadian increase in activity in anticipation of the doe's visit, which is entrained by suckling and appears analogous to feeding-entrained rhythms reported for other species. By investigating the expression of c-Fos protein in nursed and un-nursed pups at selected times before and after scheduled nursing, we were able to distinguish endogenous patterns of neuronal activation and patterns induced by suckling. Increased endogenous expression of c-Fos in the paraventricular thalamus and in the magnocellular neurons of the paraventricular hypothalamus coincided with the period of anticipatory arousal. By contrast, suckling induced c-Fos expression in the supraoptic nucleus and the parvocellular neurons of the paraventricular hypothalamus, whilst decreasing expression in the magnocellular neurons. Furthermore, the endogenous pattern of c-Fos expression was less distinct in 3-day-old compared to 7-day-old pups, suggesting maturational or experience-related influences on the neural correlates of the anticipatory arousal. In conclusion, the close correspondence between c-Fos expression and pups' endogenous rhythm of behaviour suggests that the rabbit's natural schedule of restricted nursing provides an ideal model in which to investigate the ontogeny of circadian function without disrupting the mother-offspring relationship or normal neonatal development.     

Repeated alcohol administration differentially affects c-Fos and FosB protein immunoreactivity in DBA/2J mice

To identify alcohol-responsive brain areas, we have immunohistochemically analyzed expression of c-Fos, FosB, and other Fos-related antigens in the brain of inbred DBA/2J mice after a single or repeated injection of alcohol (4 g/kg). We observed increased expression of c-Fos after alcohol administration in the central nucleus of amygdala, paraventricular nuclei of hypothalamus and thalamus, and several other brain areas. Although increased expression of c-Fos in the nucleus accumbens was also observed, this increase was not statistically significant. Repeated administration of alcohol had the tendency to reduce alcohol-induced c-Fos expression in these areas. Immunohistochemical analysis using an antibody recognizing most Fos-related antigens revealed increases of expression of these proteins in a partially overlapping set of brain regions. In contrast to c-Fos, FosB expression was found to be elevated significantly higher after repeated than after acute treatment with alcohol in several brain areas, including the shell of nucleus accumbens. In contrast to previous c-Fos studies, our studies confirm that alcohol administration indeed activates the reward circuits, including the basal ganglia, and suggest that FosB could serve as a more sensitive marker for this activation.     

Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat

Intraperitoneal (i.p.) administration of sulfated CCK octapeptide (CCK-8S) has been shown to induce changes in neuronal activity in the nucleus of the solitary tract (NTS) and area postrema (AP), sensory parts of the dorsal vagal complex (DVC), and in the paraventricular nucleus of the hypothalamus (PVN), as determined by activation of c-fos expression. Whether peripheral CCK influences neuronal activity in the locus coeruleus (LC)/subcoeruleus nucleus (SC) was investigated in awake rats at intraperitoneal (i.p.) injection of CCK-8S by c-Fos immunohistochemistry. CCK-8S i.p. (25, 50, and 100 micrograms/kg, respectively) dose-dependently increased the average number of c-Fos-LI-positive cells/section in the LC/SC by the factor 5.9, 8.2, and 11.7, respectively. Pretreatment with the CCK-A receptor antagonist MK-329 (devazepide; 1 mg/kg and 2 mg/kg i.p.) reduced the CCK-induced increase in c-fos expression in the LC/SC by 54% and 75%, respectively; the CCK-B receptor antagonist L-365,260 had no effect. Perivagal capsaicin pretreatment diminished the CCK-induced increase in the number of c-Fos-LI-positive cells in the LC/SC by 65%. In comparison, the CCK-A antagonist devazepide (1 mg/kg and 2 mg/kg i.p.) reduced the increase in c-fos expression by 76% and 88% in the PVN, 69% and 88% in the NTS, 86% and 83%, respectively, in the AP. Capsaicin diminished the CCK-induced increase in c-Fos-LI-positive cells in the PVN by 64%, in the NTS by 60%, but in the AP only by 25%. Immunostaining against the nuclear antigen c-Fos and the cytoplasmatic antigen tyrosine hydroxylase (TH) showed that 40% of all c-Fos-LI-positive cells in the LC/SC were TH-LI positive at 25 micrograms CCK/kg. The data indicate that CCK-8S i.p. induces modulation of neuronal activity in the LC/SC, DVC and PVN predominantly by peripheral action of CCK-A receptors and capsaicin-sensitive vagal afferents. These findings suggest that the LC/SC is involved in CNS-mediated regulatory influences of peripheral CCK.     

Lipopolysaccharide-induced Fos expression in hypothalamic nuclei of neonatal rats

The inability of neonates to fully evoke the acute-phase reaction to infection is thought to be due in part to central nervous system immaturity. We used the expression of Fos protein to evaluate whether acute-phase reaction deficits in neonates may indeed be linked to unresponsiveness of brain regions that mediate the responses to infection in adult animals. In this study, we used lipopolysaccharide (LPS) as the infectious agent. Rats aged 0-1, 3, 6, 9, 12 and 15 days were divided into groups treated with low- or high-dose LPS (Escherichia coli; 50 and 500 micrograms/kg, respectively, i.p.) or pyrogen-free saline (PFS) i.p. Two hours after injection, the animals were deeply anesthetized, sacrificed, and their brains removed for Fos immunocytochemistry. Fos-like immunoreactive (FLI) neurons in the preoptic area (POA), paraventricular nucleus of the hypothalamus (PVN), and organum vasculosum laminae terminalis (OVLT) were compared between the treatment and the age groups. The forebrain was devoid of FLI neurons in 1-day-old rats, but FLI neurons were present at 3 days of age and continued to increase with age until 9 days after birth. There were no significant differences between the LPS- and PFS-treated groups until day 12 of age. At 12 and 15 days of age, FLI neurons in the PVN, medial preoptic and lateral preoptic nuclei, and the area surrounding the OVLT were greater in the LPS-treated animals. The expression appeared to be both age- and dose-dependent. These observations show that the rat brain structures that participate in the mediation of the acute-phase reaction do not become responsive to systemic pyrogens until 12 days of age, thus suggesting that insensitivity of the brain to pyrogenic agents may be partly responsible for the poor response of neonates to infectious agents.     

Antinociceptive effects of RB101, a complete inhibitor of enkephalin-catabolizing enzymes, are enhanced by a cholecystokinin type B receptor antagonist, as revealed by noxiously evoked spinal c-Fos expression in rats

The effects of RB101, a complete inhibitor of enkephalin-catabolizing enzymes, alone or with a selective cholecystokinin (CCK)B receptor antagonist (CI988) or CCK(A) receptor antagonist (devazepide), on carrageenin-induced spinal c-Fos expression were investigated. Spinal c-Fos expression was observed 90 min after intraplantar carrageenin (6 mg/150 microl saline), with Fos-like-immunoreactive neurons preferentially located in the superficial laminae of the spinal dorsal horn. Intravenous RB101 (10, 20 and 40 mg/kg) dose-dependently reduced the number of superficial Fos-like-immunoreactive neurons (r2 = 0.739, P < .0001), with 63 +/- 2% (P < .0001) reduction for the highest dose. These effects were completely blocked by coadministered naloxone. Coadministration of inactive doses of i.v. RB101 (5 mg/kg) and i.p. CI988 (3 mg/kg) significantly and strongly reduced the number of carrageenin-induced, superficial, Fos-like-immunoreactive neurons (55 +/- 5% reduction of control carrageenin c-Fos expression, P < .0001). This effect was blocked by coadministered naloxone. It is important to note that coadministered RB101 and devazepide did not influence spinal c-Fos expression. None of the various drug combinations influenced the carrageenin-induced peripheral edema. These results show that RB101 dose-dependently decreases carrageenin-evoked spinal c-Fos expression. In addition, the effectiveness of RB101 can be revealed by preadministration of the CCK(B) receptor antagonist CI988. Considering the weak opioid side effects obtained with RB101 treatment and the strong increase of its effects by the CCK(B) receptor antagonist, this type of drug combination could have promising therapeutic application in the management of pain in humans.     

Effects of sinoaortic denervation on Fos expression in the brain evoked by hypertension and hypotension in conscious rabbits

We have previously shown [Li and Dampney (1994) Neuroscience 61, 613-634] that periods of sustained hypertension and hypotension each induces a distinctive and reproducible pattern of neuronal expression of Fos (a marker of neuronal activation) in specific regions of the brainstem and forebrain of conscious rabbits. The aim of this study was to determine the contribution of afferent inputs from arterial baroreceptors to the activation of neurons in these various brain regions that is caused by a sustained change in arterial pressure. Experiments were carried out on rabbits in which the carotid sinus and aortic depressor nerves were cut in a preliminary operation. Following a recovery period of seven to 10 days, a moderate hypertension or hypotension (increase or decrease in arterial pressure of 20-30 mmHg) was induced in conscious barodenervated rabbits for 60 min by the continuous infusion of phenylephrine or sodium nitroprusside, respectively. In control experiments, barodenervated rabbits were subjected to the identical procedures except that they were infused with the vehicle solution alone. Compared with the effects seen in barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] the number of neurons that expressed Fos in response to hypertension was reduced by approximately 90% in the nucleus of the solitary tract and in the caudal and intermediate parts of the ventrolateral medulla. In supramedullary regions, baroreceptor denervation resulted in a reduction of approximately 60% in hypertension-induced Fos expression in the central nucleus of the amygdala and in the bed nucleus of the stria terminalis, but no significant reduction in the parabrachial complex in the pons. Following hypotension, the number of neurons that expressed Fos in barodenervated rabbits, compared with barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] was reduced by approximately 90% in the nucleus of the solitary tract, area postrema, and caudal, intermediate and rostral parts of the ventrolateral medulla. Baroreceptor denervation also resulted in a similar large reduction in hypotension-induced Fos expression in many supramedullary regions (locus coeruleus, midbrain periaqueductal grey, hypothalamic paraventricular nucleus, and in the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the basal forebrain). In the supraoptic nucleus, hypotension-induced Fos expression in barodenervated rabbits was reduced by 75% compared to barointact animals, but was still significantly greater than in control animals. There was also a high level of Fos expression, much greater than in control animals, in the circumventricular organs surrounding the third ventricle (subfornical organ and organum vasculosum lamina terminalis). The results indicate that in conscious rabbits the activation of neurons that occurs in several discrete regions at all levels of the brain following a sustained change in arterial pressure is largely dependent upon inputs from arterial baroreceptors, with the exception of neurons in the circumventricular organs surrounding the third ventricle that are activated by sustained hypotension. The latter group of neurons are known to project to vasopressin-secreting neurons in the supraoptic nucleus, and may therefore via this pathway trigger the hypotension-induced release of vasopressin that occurs in the absence of baroreceptor inputs.     

Spatially and temporally differentiated patterns of c-fos expression in brainstem catecholaminergic cell groups induced by cardiovascular challenges in the rat

Brainstem catecholaminergic neurons have been implicated as mediating adaptive autonomic and neuroendocrine responses to cardiovascular challenges. To clarify the nature of this involvement, immuno- and hybridization histochemical methods were used to follow c-fos expression in these neurons in response to acute stimuli that differentially affect blood pressure and volume. From low basal levels, hypotensive hemorrhage (15%) provoked a progressive increase in the number and distribution of Fos-immunoreactive (ir) nuclei in the nucleus of the solitary tract (NTS), the A1 and C1 cell groups of the ventrolateral medulla, and in the pontine A5, locus coeruleus, and lateral parabrachial cell groups peaking at 2.0-2.5 hours after the challenge. Fos-ir ventrolateral medullary neurons, subsets of which were identified as projecting to the paraventricular hypothalamic nucleus or spinal cord, were predominantly aminergic, whereas most of those in the NTS were not. Infusion of an angiotensin II antagonist blunted hemorrhage-induced Fos expression in the area postrema, and attenuated that seen elsewhere in the medulla and pons. Nitroprusside-induced isovolemic hypotension yielded a pattern of c-fos induction similar to that seen following hemorrhage, except in the area postrema and the A1 cell group, where the response was muted or lacking. Phenylephrine-induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to non-aminergic neurons, whose distribution in the NTS conformed to the termination patterns of primary baroreceptor afferents, and in the ventrolateral medulla overlapped in part with those of vagal cardiomotor and depressor neurons. These findings underscore the importance of brainstem catecholaminergic neurons in effecting integrated homeostatic responses to cardiovascular challenges and their ability to responding strategically to specific modalities of cardiovascular information. They also foster testable predictions as to effector neuron populations that might be recruited to respond to perturbations in individual circulatory parameters.     

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 microl) 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.     

Ketoprofen produces profound inhibition of spinal c-Fos protein expression resulting from an inflammatory stimulus but not from noxious heat

This study assesses the anti-inflammatory/analgesic effects of ketoprofen a non-steroidal anti-inflammatory drug, using the method of c-Fos immunoreactivity at the spinal cord level in two models of noxious stimulation: carrageenan-induced inflammatory pain or acute noxious heat. Ketoprofen was pre-administered intravenously or orally 25 min before an intraplantar injection of carrageenan (6 mg in 150 microliters of saline) in hindpaw of the non-anaesthetised rat or before a single noxious heat (52 degrees C, 15 sec) stimulation of hindpaw of the anaesthetised rat. Three hours after carrageenan or 2 h after noxious heat, the number of spinal c-Fos protein-like immunoreactive (c-Fos-LI) neurons in L4-L5 segments and both the ankle and paw diameter, the indicator of peripheral oedema, were assessed. Pre-administered ketoprofen (1, 3 and 10 mg/kg i.v.) dose-dependently blocks the development of the carrageenan-induced spinal c-Fos protein expression and peripheral oedema, with the highest dose influencing in parallel both parameters (75 +/- 2% diminution of total number of c-Fos-LI neurons per L4-L5 section; 64 +/- 4% and 82 +/- 6% diminution of paw and ankle oedema, respectively). The effect of ketoprofen was significantly greater on the number of c-Fos-LI neurons in deep, as compared to superficial, laminae. Furthermore, the dose-dependent effects of ketoprofen on the carrageenan-induced spinal c-Fos protein expression and both the paw and ankle oedema were correlated. Oral pre-administration of ketoprofen (20 mg/kg) produced the blockage of development of the carrageenan-induced spinal c-Fos protein expression (65 +/- 3% diminution of total number of c-Fos-LI neurons per L4-L5 section) and peripheral oedema (20 +/- 3% and 59 +/- 10% diminution of paw and ankle oedema, respectively). In contrast, the same doses of both the intravenous and oral pre-administration of ketoprofen did not influence either the spinal c-Fos protein expression nor slightly enhanced paw diameter induced by a single noxious heat stimulation. This study suggests a predominant peripheral site, without excluding a central site of action of ketoprofen in the carrageenan-induced inflammation. The method of c-Fos protein-like immunoreactivity revealed ketoprofen to be more potent in comparison to members of other families of non-steroidal anti-inflammatory drugs, previously studied in the same experimental conditions of carrageenan-induced inflammatory pain.     

mRNAS for one, two or three members of trk receptor family are expressed in single rat trigeminal ganglion neurons

We have studied the effects of the neuroleptic haloperidol and the non-benzodiazepine anxiolytics buspirone and lesopitron on the expression of c-Fos immunoreactivity in the rat forebrain. Haloperidol and buspirone administration resulted in a significant quantitative increase in the number of Fos-immunoreactive neurons in the lateral striatum and a presumable qualitative increase in the nucleus accumbens. In contrast, lesopitron did not lead to a significant increase in the c-Fos expression in the striatum. The induction of c-Fos immunoreactivity by buspirone is compatible with an interaction of this compound with D2 dopamine receptors, as documented for haloperidol. The lack of effects after lesopitron administration suggests that, in contrast with buspirone, this compound has no dopaminergic blocking activity.