[Toward a metabolic approach of the central pattern generator concept in a spinal rat model]. / Vers une approche métabolique du centre locomoteur autonome chez l'animal: le modèle d'hémisection médullaire chez le rat.

It has been shown that the onset of a central nervous system lesion in the rat results in morphological modifications of the peripheral nerves and the underlying neuromuscular junctions, without suggesting a functional correlation between recuperation of motor functions and sublesional metabolic activity. Using double lesion localization (T2 and T6) in a spinal rat model has nevertheless pointed out the functional importance of the T2-T6 metameric interval in the reinnervation phenomena observed, raising the problem of spinal generation in locomotor movements. Motivated by electrophysiological data that have given support to the concept of an anatomic substrate for these intramedullary rhythm generators, we attempted to establish a relation between the functional recuperation possible after a central nervous system lesion and modifications within the metabolism of the underlying neuromuscular system. We notably focused on Na/K-ATPase, whose crucial role in neuromuscular transmission has been evidenced. This paper proposes to demonstrate the involvement in the mechanisms of metabolic regulation after trans-synaptic denervation, i.e., a central nervous system lesion. Our study includes the Na/K-ATPase activity analysis on the sublesional peripheral nerve and the combined analysis of the expression of different RNA messengers within the corresponding muscle groups. We have also investigated the spatiotemporal organization of the compensating processes of the nerves underlying the lesion using magnetic resonance spectroscopy.

Leptin responsiveness in chronically decerebrate rats.

Peripheral infusions of physiological doses of leptin decrease body fat mass, but it is not known whether this results from direct effects on peripheral tissue or activation of central leptin receptors. In this study, we infused chronically decerebrate (CD) rats, in which the forebrain was surgically isolated from the caudal brainstem, with 60 microg leptin/d or PBS for 14 d from ip mini-osmotic pumps. The CD rats were tube fed an amount of food equivalent to the intake of ad libitum-fed intact controls or 75% of this amount to account for their reduced energy expenditure. Control rats fed ad libitum or tube fed 75, 100, or 125% of their ad libitum intake also were peripherally infused with leptin or PBS. CD rats had a lower serum testosterone, energy expenditure, and lean body mass compared with controls but had increased levels of adiponectin and leptin and were obese. Leptin increased body fat and decreased energy expenditure during the light period in 100%-fed CD rats, but not 75%-fed CD rats. Leptin decreased body fat of ad libitum- and 100%-fed but not 75%-fed or 125%-fed intact controls. Energy expenditure did not change in any control group. These results show that leptin can change body fat independent of a change in food intake or energy expenditure, that the forebrain normally prevents leptin from inhibiting energy expenditure through mechanisms initiated in the caudal brainstem or peripheral tissues, and that the leptin response in both intact and CD rats is determined by the energy status of the animal.

Involvement of forebrain in parabrachial neuronal activation induced by aversively conditioned taste stimuli in the rat.

We previously have shown that forebrain inputs increase responses of amiloride-sensitive NaCl-best neurons to the conditioned stimulus (CS) in the rat parabrachial nucleus (PBN) after the establishment of conditioned taste aversion (CTA) to NaCl. In the present study, we examined the effects of aversively-conditioned NaCl taste stimulation on Fos-like immunoreactivity (FLI) in the PBN using awake intact and decerebrate rats. In Experiment 1, the CTA-trained and sham-conditioned control rats were intraorally infused with 0.1 M NaCl or 0.1 M NaCl mixed with 10(-4) M amiloride, a sodium-channel blocker. Significantly more NaCl-stimulated FLI was observed in the central medial (cms) and external lateral subnuclei (els) of PBN in the CTA-trained group than in the control group. In both groups, amiloride markedly reduced NaCl-stimulated FLI in the cms but not in the els. In Experiment 2, we found that after decerebration, there was no significant difference in FLI between the CTA-trained and sham-conditioned groups. These results suggest that (1) amirolide-sensitive taste information of NaCl projects mainly to the cms; (2) sensory information of aversive taste stimuli is likely to be represented in the els; and (3) forebrain inputs are required for elevated FLI in the PBN after CTA.

MODULATION OF THE MONOSYNAPTIC REFLEX POTENTIALSIN THE DECEREBRATED RATS UNDER THE INFLUENCE OF HYDROXYTRYPTOPHAN.

We studied the serotonin effect on monosynaptic reflex potentials (MSR) of spinal motorneurons in the decerebrated rats in control and after intraperitoneal administration of serotonin precursor ­ 5-Hydroxytryptophan (5-HTP). MSR of motorneurons in the lumbar spinal cord were registered using electrical stimulation of dorsal root of the 5th lumbar section. During stimulation physiological saline or 5-hydroxytryptophan was injected intraperitoneally. In comparison with average amplitude of the control MSR there were registered significant increase in amplitudes of the MSR (169% and +172%, P <0,001) in animals with injection 5-HTP. These data suggest that serotonin release after 5-HTP administration leads to activation of motorneurons in the lumbar spinal cord. The mechanism of this activation may be related to the weakening of the inhibitory control of interneurons in the transmission pathways of the excitatory influences from muscle afferent to motorneurons and to the postural (antigravity) reflex reactions which necessary for the initiation of locomotion.

Effect of unilateral noise exposure on the tonotopic distribution of spontaneous activity in the cochlear nucleus and inferior colliculus in the cortically intact and decorticate rat.

Effects of unilateral noise exposure on spontaneous activity (SA) in the anteroventral and dorsal cochlear nuclei (AVCN and DCN) and the central nucleus of the inferior colliculus (ICc) were studied in cortically intact and decorticate rats. SA was measured 1 week following exposure using uptake of 14C-labeled 2-deoxyglucose (2DG) in quiet. Optical density (OD) measurements were obtained in low- and high-frequency (LF and HF) areas of each nucleus. We refer to the ipsilateral AVCN and DCN (side of the noise-exposed ear) and the contralateral ICc as direct nuclei and to their opposite side counterparts as indirect nuclei. Noise exposure altered the tonotopic profile of SA in the direct pathway by causing a decrease in the ratio of HF OD to LF OD (HF/LF ratio). In intact animals, the decreased HF/LF ratio was due to decreased HF OD. In decorticate animals, it was due to decreased HF OD and increased LF OD, the latter occurring mainly in the DCN and ICc. Decorticate-intact differences may reflect corticofugal feedback inhibition. Lesion of the dorsal acoustic stria caused a substantial decrement of SA in the contralateral ICc. Furthermore, strong positive correlations between HF/LF ratios in the DCN, AVCN, and contralateral ICc suggest that the cochlear nucleus is a major contributor to SA in the ICc. Noise exposure had opposite and weaker effects on 2DG uptake in the indirect pathway that were attributed to crossed inhibition. Noise-induced changes in the tonotopic profile of SA may represent a neural correlate of tinnitus.

Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat.

Central administration of melanocortin 3 and 4 receptor (MC3/4-R) agonists increases energy expenditure, with the hypothalamus commonly held as the primary site of action. It is also clear, however, that MC4-R are expressed in caudal brainstem structures of relevance to the control of energy expenditure. Three experiments investigated whether hindbrain MC-R contribute to the energy expenditure effects of central MC3/4-R agonist treatments; in each, we examined the effect of fourth intracerebroventricular (i.c.v.) administration of a MC3/4-R agonist, MTII (three injections, each separated by 12 h), on uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue (BAT). First, we compared the effects of fourth and third i.c.v. administration of MTII and found that the hindbrain and forebrain treatments were equally effective at elevating UCP-1 mRNA expression in BAT compared with the respective vehicle-treated group results. A second experiment demonstrated that the fourth i.c.v. MTII-induced rise in UCP-1 expression was mediated by sympathetic outflow to BAT by showing that this response was abolished by surgical denervation of BAT. In the third experiment, we showed that chronic decerebrate rats, like their neurologically intact controls, elevated UCP-1 mRNA expression in response to fourth i.c.v. MTII administration. Taken together, the results indicate that: 1) there is an independent caudal brainstem MC3/4-R trigger for a sympathetically stimulated elevation in BAT UCP-1 gene expression, and 2) the MTII-induced rise in UCP-1 expression can be mediated by circuitry intrinsic to the caudal brainstem and spinal cord.

Excitotoxicity is required for induction of oxidative stress and apoptosis in mouse striatum by the mitochondrial toxin, 3-nitropropionic acid.

Excitotoxicity is implicated in the pathogenesis of several neurologic diseases, such as chronic neurodegenerative diseases and stroke. Recently, it was reported that excitotoxicity has a relationship to apoptotic neuronal death, and that the mitochondrial toxin, 3-nitropropionic acid (3-NP), could induce apoptosis in the striatum. Although striatal lesions produced by 3-NP could develop through an excitotoxic mechanism, the exact relationship between apoptosis induction and excitotoxicity after 3-NP treatment is still not clear. The authors investigated the role of excitotoxicity and oxidative stress on apoptosis induction within the striatum after intraperitoneal injection of 3-NP. The authors demonstrated that removal of the corticostriatal glutamate pathway reduced superoxide production and apoptosis induction in the denervated striatum of decorticated mice after 3-NP treatment. Also, the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, prevented apoptosis in the striatum after 3-NP treatment for 5 days, whereas the non-NMDA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, was ineffective. The authors also evaluated the initial type of neuronal death by 3-NP treatment for different durations from 1 to 5 days. In early striatal damage, apoptotic neuronal death initially occurred after 3-NP treatment. Our data show that excitotoxicity related to oxidative stress initially induces apoptotic neuronal death in mouse striatum after treatment with 3-NP.

Pharmacology of M & B 18,706, a drug which selectively reduces decerebrate rigidity.

1 (+/-)-10-(3-Dimethylamino-2-methylpropyl)-2-valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chloropromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation.2 When given intravenously M & B 18,706 had seven times the potency of dimethothiazine and one-half the potency of chlorpromazine in reducing the rigidity of the intercollicular decerebrate cat. When administered orally M & B 18,706 and chlorpromazine were equi-potent in reducing rigidity but M & B 18,706 was less effective than chlorpromazine in producing ataxia in this species.3 In the rat, M & B 18,706 had one-quarter the potency of chlorpromazine for reducing decerebrate rigidity but had from 1/20th to 1/200th its potency in tests for sedative or tranquillizing activity.4 M & B 18,706, like dimethothiazine and chlorpromazine, had little effect on the rigidity of ischaemic decerebrate cats and failed to inhibit polysynaptic spinal reflexes.5 M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat.

Decortication and striatal mRNA: increases of mRNA for fibronectin, but not of NCAM or alpha-1 tubulin.

Ipsilateral frontal cortex lesions damaged the corticostriatal input. Northern hybridization analysis showed increases in fibronectin (FN) mRNA, but not changes in mRNA for neural cell adhesion molecule (NCAM), neuro-filament-68 (NF-68) or alpha-tubulin (alpha-1T) 72 h post-lesion. In situ hybridization resolved a different spatial-temporal distribution. The superficial cell layer beneath the wound cavity showed transient elevations of FN mRNA that peaked at 72 h post-lesion. However, in the ipsilateral striatum, FN mRNA was maximal at later times than in the wound cavity, at 240 h post-lesion. Changes in NCAM and alpha-tubulin mRNAs in response to decortication occur only around the wound cavity but not in the deafferentated striatum. The different time courses of mRNA revealed by Northern blot analysis and in situ hybridization are most probably due to contamination of the ipsilateral striatum at dissection with superficial tissue adjacent to the wound cavity. These results suggest that cellular responses to ipsilateral decortication consist of two phases: (i) a wound healing process; and (ii) striatal responses to deafferentation.

Cholecystokinin is released from a crossed corticostriatal pathway.

The release of striatal cholecystokinin, glutamate, aspartate and dopamine was studied in vivo with microdialysis in decorticated rats, with or without callosotomy. Unlesioned rats were also analysed. Unilateral decortication produced a unilateral decrease in K(+)-stimulated extracellular striatal glutamate and aspartate levels, without decreasing cholecystokinin or dopamine levels. However, following decortication plus callosotomy, basal and K(+)-stimulated extracellular cholecystokinin and glutamate levels were significantly decreased in the striatum ipsilateral to side of decortication. Aspartate levels were bilaterally decreased. These results give evidence for the existence of crossed corticostriatal projections containing releasable cholecystokinin and glutamate.

BDNF down-regulates the caspase 3 pathway in injured geniculo-cortical neurones.

Visual cortex ablation in newborn rats causes a rapid and almost complete degeneration of neurones in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of geniculo-cortical fibres. Death of dLGN neurones occurs by apoptosis and is partially prevented (approximately 50%) by intraocular delivery of brain-derived neurotrophic factor (BDNF). Here we investigated the molecular mechanisms of BDNF-mediated neuroprotection. We found that exogenous administration of BDNF partially decreases (approximately 50%) the up-regulation of apoptotic proteins (phosphorylated c-Jun, cytochrome C and cleaved caspase 3), that occurs in dLGN neurones following visual cortex ablation at postnatal day 7. These results demonstrate that the neuroprotective action of BDNF on axotomised dLGN neurones involves the partial blockade of well-characterised apoptotic pathways.

Bronchomotor responses to hypoxia and hypercapnia in decerebrate cats.

Decerebrate animals are often used in investigations of the control of breathing because anesthesia-induced depression of respiratory reflexes is absent. We therefore investigated the level of tone and responsiveness of airway smooth muscle in seven decerebrate, paralyzed, and ventilated cats. Specifically, we measured the changes in pulmonary resistance (RL) and dynamic pulmonary compliance (CLdyn) in response to hypoxia and hypercapnia. All cats responded to hypoxia (approximately 10% O2 in N2) with significant increases (mean 49%, range 5-156%) in RL from a mean control value of 0.0197 +/- 0.0081 (SD) cmH2O.ml-1.s. During inhalation of 5% CO2 in O2, RL increased significantly (mean 59%, range 16-135%) from a mean control value of 0.0190 +/- 0.0056 cmH2O.ml-1.s. Decreases in CLdyn during hypoxia and hypercapnia were much smaller, averaging -9 and -11%, respectively. After atropine was administered, average control RL fell 50%, from 0.0269 to 0.0134 cmH2O.ml-1.s (P < 0.05; n = 4). Hypoxic and hypercapnic gas mixtures did not affect pulmonary mechanics after atropine was administered. In three cats, oscillations of RL were synchronized to phrenic activity but only at low respiratory frequencies (approximately 12 cycles/min), indicating that airway smooth muscle responded slowly to vagal input. Pentobarbital sodium, like atropine, reduced control RL in three cats. These cats lost their bronchoconstrictor response to hypercapnia but had augmented responses to hypoxia compared with preanesthetic responses. We conclude that decerebrate cats possess resting bronchomotor tone and retain their responsiveness to hypoxia and hypercapnia. Thus the decerebrate cat is a useful model for studying the control of tracheobronchial smooth muscle.

A comparison between microwave irradiation and decapitation: basal levels of dynorphin and enkephalin and the effect of chronic morphine treatment on dynorphin peptides.

Opioid peptides were analysed in tissue extracts of various brain structures and the pituitary gland from rats sacrificed by microwave irradiation, and compared with peptide levels in tissue extracts from decapitated rats. Dynorphin A, dynorphin B and Leu-enkephalinArg6, derived from prodynorphin, and Met-enkephalinArg6Phe7 from proenkephalin, were measured. Basal immunoreactive levels of dynorphin A and B were consistently higher in extracts from microwave-irradiated rats, whereas in these extracts immunoreactive levels of Leu-enkephalinArg6, an endogenous metabolite of dynorphin peptides, were either lower than, the same as or higher than in decapitated rats. Immunoreactive levels of Met-enkephalinArg6Phe7 were higher in microwave-irradiated rats. Effects of morphine treatment on prodynorphin peptide levels were evaluated and compared with previous findings in decapitated rats. Dynorphin immunoreactive levels were higher in the nucleus accumbens and striatum of morphine-tolerant rats than in corresponding areas in saline-treated rats. These results indicate tissue-specific metabolism of prodynorphin peptides and show that metabolism of opioid peptides occurs during the dissection procedure after decapitation of the rat even though precautions are taken to minimize degradation.

Cortical acetylcholine efflux with hypercapnia and nociceptive stimulation.

In rabbits anesthetized with 70% N2O-30% O2, the rate of efflux of acetylcholine (ACh) from the cerebral cortex doubled during hypercapnia (increase of end-tidal CO2 from 4 to 8%), and during mild nociceptive stimulation of the tail. Under 0.7% halothane anesthesia, the control rate of ACh efflux was lower than that under N2O; the rate rose 2-fold during hypercapnia and 4-fold during tail stimulation. In the absence of systemic atropinization, increase in ACh efflux was correlated with a shift in EEG from high- to low-voltage ('activated'); after systemic atropinization EEG remained in the high-voltage state, but the changes in ACh efflux with hypercapnia and stimulation were not affected. Following transection of the midbrain, ACh efflux was markedly depressed and did not change during hypercapnia. Taken in context with the previously known facts that the cerebral hyperemia of hypercapnia is potentiated by cholinesterase inhibition and attenuated by atropine or decerebration, the present results support the concept of a cholinergic regulation of the cerebral vasculature.

A comparison of cathepsin B processing and distribution during neuronal death in rats following global ischemia or decapitation necrosis.

The objective of this study was to examine the possible role of the cysteine protease cathepsin B (E.C. 3.4.22.1) in the delayed neuronal death in rats subjected to the two-vessel occlusion model of global ischemia. Immunohistochemistry of the hippocampus showed an alteration in the distribution of cathepsin B in CA1 neurons from a lysosomal pattern to a more intense label redistributed into the cytoplasm. This change was not detected until the neurons had become morphologically altered with obvious shrinkage of the cytoplasmic region. Western blotting and enzyme activity measurements of subcellular fractions, including lysosomes and a cell soluble fraction, demonstrated that there was an overall decrease in cathepsin B activity at this time but an increase in the proenzyme form, particularly in the soluble fraction. This was found to be completely different from the marked loss of all forms of cathepsin B in necrotic neurons following decapitation.

Mesopontine contribution to the expression of active 'twitch' sleep in decerebrate week-old rats.

Myoclonic twitching is a ubiquitous feature of infant behavior that has been used as an index of active sleep. Although the active sleep of infants differs in some ways from the REM sleep of adults, their marked similarities have led many to view them them as homologous behavioral states. Recently, however, this view has been challenged. One avenue for resolving this issue entails examination of the neural substrates of active sleep. If the neural substrates of active sleep were found to be similar to those of REM sleep, then this would support the view that the two states are homologous. Therefore, in the present study, decerebrations were performed in the pons and midbrain to determine whether the mesopontine region is important for the expression of active sleep in infants, just as it is for the expression of REM sleep in adults. It was found that, in comparison to controls, caudal pontine decerebrations reduced myoclonic twitching by 76%, rostral pontine decerebrations reduced twitching by 40%, and midbrain transections had no significant effect on twitching. Moreover, analysis of the temporal organization of twitching indicated that pontine decerebrations predominantly affected high-frequency twitching while leaving unaffected the low-frequency twitching that is thought to be contributed by local spinal circuits at this age. These results indicate that the mesopontine region plays a central role in the expression of active sleep in infant rats.

Cardiovascular responses to chemical stimulation of the lateral tegmental field and adjacent medullary reticular formation in the rat.

Relatively few studies have been done to characterize cardiovascular responses to the chemical stimulation of sites located in the medullary lateral tegmental field (LTF) and most of them have been carried out in anesthetized animals. Our experiments were carried out in decerebrated, artificially ventilated, adult male Wistar rats. In the LTF, two types of cardiovascular responses were elicited. One type consisted of pressor responses accompanied by bradycardia. Such responses were elicited from a region 0.4 mm caudal to 0.8 mm rostral to the calamus scriptorius (CS); maximum responses were elicited from a site 0.6 mm rostral to the CS, 1.2 mm lateral to the midline and 1.2 mm deep from the dorsal medullary surface. Another type consisted of pressor responses without any change in heart rate; such responses were elicited from a region 1-1.6 mm rostral to the CS. Nucleus ambiguus (nAmb) and dorsal motor nucleus of the vagus (nDMX) and the reticular formation surrounding these areas were the main sites from which bradycardia (accompanied by either no or small changes in BP) was elicited. In the nAmb, maximum bradycardia was elicited from a site 0.6 mm rostral to the CS, 1.8 mm lateral to the midline and 2.4 mm deep from the dorsal medullary surface. In the nDMX, most prominent bradycardic responses were elicited at 0-0.6 mm rostral to the CS, and 0.6 mm lateral to the midline and 1 mm deep from the dorsal medullary surface. Cardiovascular effects elicited from sites in other well-known areas, such as the rostral ventrolateral medullary pressor area (RVLM) and caudal ventrolateral medullary depressor area (CVLM), and the nucleus tractus solitarius (nTS) were also included for comparison of different responses. These results are expected to prove useful in studies in which the microinjection technique is used to characterize cardiovascular responses.

Opioids induce postural asymmetry in spinal rat: the side of the flexed limb depends upon the type of opioid agonist.

The kappa-agonists bremazocine and dynorphin(1-13), the sigma-agonist SKF 10.047 as well as the delta-agonists [D-Ala2,D-Leu5]-enkephalin (DADL) and Met-enkephalin, but not the mu-agonist morphine, applied subarachnoidally to the caudal portion of the transected spinal cord (at the T3-T4 level) induced postural asymmetry of the hind limbs in rats. Asymmetry was registered visually. The leg was regarded as flexed if its projection on the longitudinal axis of the animal was smaller than that of its counterpart. The side of the flexed leg depended upon the type of drug: bremazocine, dynorphin(1-13) and Met-enkephalin predominantly induced flexion of the right leg, SKF 10.047 induced flexion of the left leg (at some doses there is no side preference), while in the case of DADL the side of the flexed leg depended upon the dose of the drug. Comparison of electromyographic activity of the symmetric biceps and quadriceps femoris revealed that bremazocine considerably facilitates the flexion reflex of the right hind limb without affecting the left limb reflex. As a rule, a flexed leg determined visually exhibited higher EMG activity of the biceps femoris as compared with a symmetric one. The opiate antagonist naloxone significantly reduced the percentage of animals with postural asymmetry. The magnitude of asymmetry and the side of flexion were not constant in some animals, but changed with time. However, the mean magnitude of asymmetry, the percentage of animals with asymmetry and the left/right flexion ratio in each group of animals remained constant. The side of flexion also depended upon the level of spinal cord transection: bremazocine and Met-enkephalin injected subarachnoidally following transection at the T1-T4 and T5-T6 levels predominantly induced flexion of the right and the left leg, respectively. Asymmetry did not develop in physiologically intact animals given bremazocine, even if the spinal cord was cut later, i.e. transection of the spinal cord was necessary for the development of asymmetry. These data indicate that the neurons which maintain muscular tone of the hind limbs and which are located symmetrically to the sagittal plane, have different sensitivities to kappa-, sigma-, and delta-agonists. In most animals, neurons with a higher specificity to some agonist are localized on one side of the sagittal plane.

Cardiovascular responses to microinjections of glutamate into the nucleus tractus solitarii of unanesthetized supracollicular decerebrate rats.

In anesthetized rats, microinjections of excitatory amino acids (EAAs) into the nucleus tractus solitarii (nTS), in a region located immediately rostral to the calamus scriptorius (CS), have been generally reported to elicit depressor and bradycardic responses. On the other hand, in conscious freely moving rats, similar microinjections have been reported to elicit pressor and bradycardic responses. These divergent results have been attributed to the effect of anesthetics. A reinvestigation of the effects of EAAs into the nTS in unanesthetized animals became necessary in order to resolve this controversy. The microinjection technique used in freely moving conscious rats suffers from several technical limitations; for example, microinjections cannot be delivered stereotaxically. In order to avoid these limitations, the present experiments were carried out in unanesthetized supracollicular decerebrate rats. A systematic mapping of nTS in these rats, using microinjections of the solutions of EAAs in artificial cerebrospinal (aCSF) fluid, confirmed that depressor and bradycardic responses are elicited from all the sites in the nTS extending from the CS to a level about 1 mm rostral to it. Pressor responses were elicited by microinjections of l-glutamate (l-Glu) only from the chemoreceptor projection site (a region of the commissural subnucleus, 0.1-0.5 mm caudal to the CS, 0-0.5 mm lateral to the midline and 0.4-0.5 mm deep from the medullary surface). The pressor responses elicited from the aforementioned site were accompanied with bradycardia; this response may be due to diffusion of l-Glu to the dorsal motor nucleus of vagus because the bradycardia disappeared when the depth of the microinjection was reduced to 0.3, instead of 0.5 mm, from the dorsal medullary surface. When urethane was administered intravenously in unanesthetized decerebrate rats, the responses to microinjections of l-Glu remained unchanged, i.e., depressor and bradycardic responses were elicited from all the sites in the nTS extending from the CS to a level about 1 mm rostral to it and pressor and tachycardic responses were elicited from the chemoreceptor projection site. These observations indicated that there is no anesthetic-induced qualitative alteration of the cardiovascular responses to microinjections of EAAs into the nTS.

Brain fos-like immunoreactivity in chronic decerebrate and neurologically intact rats given 2,5-anhydro-D-mannitol.

Injection of the fructose analogue, 2,5-anhydro-d-mannitol (2,5-AM), increases food intake and Fos-like immunoreactivity (Fos-li) in both brainstem and forebrain structures. Because of the interconnections between brainstem and forebrain areas, it has not been possible to determine whether or to what extent induction of Fos-li in a given region reflects brainstem-forebrain interactions. We addressed this issue using chronic decerebrate (CD) rats with complete transections of the neuroaxis at the meso-diencephalic juncture. CD and neurologically intact control rats were injected (i.p.) with saline or 400 mg/kg 2,5-AM and brains were examined for Fos-li. Both intact and CD rats showed increased Fos-li in the nucleus of the solitary tract (NTS) after injection of 2,5-AM as compared with saline. 2, 5-AM treatment increased Fos-li in the external lateral division of parabrachial nucleus (PBNel) in intact but not in CD rats, suggesting that descending projections from the forebrain may play a role in the activation of PBNel neurons after 2,5-AM injection. Decerebration eliminated significant 2,5-AM-induced Fos-li responses in forebrain structures, including the paraventricular nucleus, supraoptic nucleus, bed nucleus of the stria terminalis and central nucleus of the amygdala. The results are consistent with the hypothesis that the activation of forebrain structures after 2,5-AM treatment is due to stimulation by ascending projections from the brainstem.