Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.     

Asymmetry of Characteristics of the Background Activity of Neurons of the Medial Vestibular Nucleus in Rats After Long-Term Vibration

Using computer analysis, we compared characteristics of the impulse background activity (BA) generated by neurons in the right and left medial vestibular nuclei (MVN) of the rats under control conditions and on the 5th, 10th, and 15th day with everyday 2-h-long sessions of vibrational stimulation. In the control group, the BA frequency generated by left-side MVN neurons was, on average, higher than that in the right MVN (23.6 ± 1.5 and 16.6 ± 1.7 sec^-1, respectively); other main characteristics of the BA demonstrated no significant internuclear differences. Vibrational influences of different durations induced complex significant laterally specific modifications of the level of regularity and dynamic indices of BA generated by neurons of the right and left MVN, of proportions of the cells with different types of distribution of interspike intervals (ISI), and of coefficients of variations of ISI. The mean frequency of background spiking in the right MVN increased about twofold (to 31.6 ± 2.2 sec^-1) after 10 days with vibration sessions, but dropped on the 15th day to 20.6 ± 1.7 sec^-1. In the left MVN, the mean BA frequency monotonically decreased, to 11.6 ± 1.0 sec^-1 after 15 days with vibration sessions. Therefore, chronic vibrational stimulation results in differential shifts of the characteristics of the BA generated by neurons of two MVN and in the formation of a new significantly asymmetrical pattern of such activity. Possible reasons for lateral asymmetry of the impulsation of MVN neurons and modifications of this asymmetry after long-term vibrational influences are discussed. We suppose that such an asymmetry can be one of the factors responsible for the development of motor and autonomic manifestations of vibration-induced motion sickness.     

眼镜蛇毒对大鼠延髓一氧化氮合酶表达的影响

目的 探讨眼镜蛇毒对大鼠延髓某些核团一氧化氮合酶(NOS)表达的影响。方法 采用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶(NADPH-d)方法,观察大鼠延髓某些核团NOS阳性神经元在眼镜蛇毒中毒组、生理盐水组、正常对照组的变化。结果 蛇毒组大鼠延髓的中缝大核,外侧网状核NOS阳性神经元比对照组表达增强。结论 眼镜蛇毒对延髓的NOS阳性神经元表达有上调作用。     

Proline Rich Polypeptide (PRP-1) Increases the Superoxide-Producing and Ferrihemoglobin Reducing Activities of Cytochrome B<Subscript>558</Subscript> Isoforms from Human Lymphosarcoma Tissue Cells

The two cytochromes (cyt) b₅₅₈ of acidic nature, one—95–100 kDa and another one, 60–70 kDa were isolated for the first time from the human’s lymphosarcoma tissue cells using gel filtration and ion exchange chromatography. These hemoproteins possess NADPH dependent O₂ ⁻-producing and ferrihemoglobin-reducing activities. The incubation of neuropeptide PRP-1 (5 μg) with cytochrome b₅₅₈, caused elevation of these activities. The gel filtration results indicated possible binding of PRP-1 to these cytochromes b₅₅₈. PRP-1 activated both NADPH dependent O₂ ⁻-producing and ferriHb-reducing activities of the cyt b¹ ₅₅₈ and cyt b² ₅₅₈, obtained from human lymphosarcoma tissue cells. One can assume that PRP-1 associated with cyt b₅₅₈ on the surface of the tumor cells by increasing both NADPH dependent O₂ ⁻-producing and ferriHb-reducing activities of cyt b₅₅₈, increases the oxidation- reduction status. Changing the oxidation–reduction status and oxygen homeostasis of the tumor cells by PRP-1 can serve as one of the possible explanation of antitumorigenic effect of this cytokine.     

眼镜蛇毒对大鼠脑桥前庭神经核nNOS表达的影响

目的 观察眼镜蛇毒对大鼠脑干神经元型一氧化氮合酶(nNOS)表达的影响,探讨其对前庭神经核的作用.方法 采用免疫组织化学方法,观察nNOS阳性细胞在眼镜蛇毒组、生理盐水组、正常对照组大鼠前庭神经核中的表达,并对其作比较.结果 蛇毒组前庭神经核nNOS表达与正常对照组、生理盐水组比较有明显下调(P＜0.01);蛇毒组前庭神经核nNOS阳性细胞灰度值与正常对照组、生理盐水组比较明显增高(P＜0.01),蛇毒对前庭神经核nNOS阳性细胞形态影响不明显.结论 眼镜蛇毒对前庭神经核nNOS表达呈下调作用.     

Acid phosphatase activity in hemolymph of the migratory grasshopper,Melanoplus sanguinipes, duringBeauveria bassiana infection

The distribution and abundance of acid phosphatase (AP) in hemolymph (HL), plasma (PM) and hemocyte lysate supernatant (HLS) of the migratory grasshopper,Melanoplus sanguinipes infected withBeauveria bassiana (strain GK 2016) has been examined. AP activity was determined at intervals from 30 min to 60 h postinjection of 2 μl of 1×10⁸ conidia/ml per grasshopper. The enzyme was detected with the substrate β-glycerophosphate in sodium acetate acetic acid buffer form hemocytes (HC) and withp-nitrophenol phosphate sodium salt for HL, PM and HLS. In results of experiment 1 proportion of HC showing AP activity increased 1–2 h, then returned to normal after 4 h. However, inB. bassiana-injected grasshoppers, a second increase was noted 24 h later which was not seen in the Tween-80-injected insects. Uninjected controls showed no change with time in the proportion of HC with AP activity. Studies were also made of the distribution of AP activity in the HL, PM, and HLS. AP activity in HL appeared to vary with the sex of the grasshoppers. Females showed increase in AP activity in HL 18–24 h after injection withB. bassiana, whereas males only showed an increase 1 h after injection. Assay of HLS showed that the level of AP activity did not change significantly throughout the experiment. Changes in AP activity in PM, in bothB. bassiana — and Tween-80-injected insects (both sexes) paralleled those of the HL, indicating that the enzyme is released from the HC. The observations are discussed in terms of the possible role of AP in the immune response ofM. sanguinipes.     

眼镜蛇毒对大鼠脊髓乙酰胆碱酯酶表达的影响

目的 探讨眼镜蛇毒对大鼠腰髓乙酰胆碱酯酶（AchE）表达的影响。方法 将蛇毒注射到大鼠左小腿下部,采用亚铁氰化铜法示AchE,观察大鼠腰髓前角AchE阳性神经元在眼镜蛇毒中毒组、生理盐水组、正常对照组的变化。结果 蛇毒组大鼠AchE阳性神经元比对照组表达增强。结论 眼镜蛇毒对腰髓的AchE阳性神经元表达有上调作用。     

Effect of Hypothalamic Proline-Rich Peptide (PRP-1) on Neuronal and Bone Marrow Cell Apoptosis

The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects including immunoregulatory, hematopoietic, antimicrobial and anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin-induced bone marrow granulocyte- and monocyte apoptosis. The intention was to further characterize the effect of PRP-1 on the survival rate of neurons and in context with myelopoiesis. We demonstrate that PRP-1 significantly reduced apoptosis of postnatal hippocampal cells induced by staurosporine. The protective effect of PRP-1 against apoptotic cell death was shown to be both time- and dose-dependent. Neuroprotection was more pronounced after prolonged pretreatment of the cells with PRP-1 before the induction of apoptosis with staurosporine. The related peptide [arg⁸]vasopressin did not reveal neuroprotection. PRP-1 also significantly reduced apoptosis of bone marrow monocytes and granulocytes induced by doxorubicin. This protective effect lasted for 2-4 h and was not detectable anymore after 24 h when PRP-1 and doxorubicin were added simultaneously. Previously obtained data and results of the current studies suggested that the hypothalamic PRP-1 possibly represents an endogenous peptide whose primary functions are to regulate myelopoiesis and neuron survival as we provide evidence that PRP can differentially reduce both staurosporine- and doxorubicin-induced hippocampal and bone marrow cell apoptosis.     

Effect of ethanol on base activity of neurons of the lateral vestibular nucleus in the cat

Experiments with cats immobilized with arduane showed that a single intravenous injection of ethanol (1 g/kg) affects 95% of the neurons of the lateral vestibular nucleus. In 56.5% of the neurons that have predominantly high-frequency base activity of the continuously arrhythmic type, injecting ethanol decreased impulse frequency by 84–93%. In 14.5% of the cells, mainly with bundle-group type activity, there was first an increase in average discharge frequency, the duration of the bundles and number of impulses in them, were replaced by a sharp inhibition of base activity, even complete suppression, in 20–30 min after ethanol injection. In 23.6% of the neurons, predominantly with an initial low frequency of base activity, a clear excitation effect developed and was recorded over the whole period of observation. Restoration of base activity to the original level usually did not occur even after 90 min. Repeated injection of the same dose of ethanol had a cumulative effect.Ivano-Frank Medical Institute, Ukrainian Ministry of Public Health. Translated from Neirofiziologiya, Vol. 24, No. 2, pp. 145–151, March–April, 1992.     

Effects of Salicylic Acid and Its Salts on Electrical Activity of Neurons of <Emphasis Type="Italic">Helix albescens</Emphasis>

We studied changes in the parameters of electrical activity of identified neurons of the parietal ganglion, PPa1 and PPa2, and of non-identified cells of the visceral ganglion (VG) of the snail Helix albescens; these changes were caused by application of salicylic acid and its salts (cobalt and zinc salicylates, CS and ZS, respectively). The above substances began to modify significantly the functional state of the neurons under study when applied in concentrations of 10⁻⁴ to 10⁻³ M. Salicylic acid suppressed the activity of all studied neurons. Application of salicylic acid in the concentration of 10⁻³ M led to a decrease in the impulsation frequency of VG neurons by factors of 1.2 to 1.5 and to an increase in the duration of AP (on average, by 2.8 ± ± 0.6 msec). In PPa1 and PPa2 cells, we observed increases in both the AP duration (by 2.4 ± 0.8 and 3.6 ± ± 1.3 msec, respectively) and that of postactivation hyperpolarization (by 29.8 ± 11 0 and 39.6 ± 9.4 msec). In the concentration of 10⁻² M, salicylic acid completely but relatively reversibly suppressed the impulse activity of all the neurons under study, causing deep hyperpolarization of their membranes. Salts of this acid, CS and ZS, demonstrated significant modulatory effects on the activity of the studied neurons; these substances initiated or enhanced the grouping of APs in bursts and also increased the AP duration. Application of 10⁻³ M CS resulted in an increase in the AP duration by, on average, 2.75 ± 0.4 msec (only in the PPa2 neuron), whereas 10⁻³ M ZS exerted analogous effects on both above neurons (in PPa1, by 2.7 ± 0.4, while in PPa2, by 3.1 ± 0.6 msec). In the case where the tested salicylates were applied in the concentration of 10⁻² M, the AP duration increased in all the cells under study (on average, by 11.8 ± 2.46 msec in VG neurons, and by 7.0 ± ± 0.4 and 7.8 ± 1.2 msec in PPa1 and PPa2 cells, respectively). With application of CS, analogous values determined by application of ZS were 14.6 ± 4.6, 6.8 ± 0.54, and 9.0 ± 0.89 msec. We assume that the modulatory effects of salicylates are mediated by their influence on the intracellular system of cyclic nucleotides. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 142–150, March–April, 2005.     

Molecular mechanisms of Brainstem plasticity

Vestibular compensation is the process of behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (unilateral labyrinthectomy, UL). Since UL results in a permanent loss of vestibular input from the ipsilateral vestibular (VIIIth) nerve, vestibular compensation is attributed to CNS plasticity and has been used as a general model of lesion-induced CNS plasticity. Behavioral recovery from the ocular motor and postural symptoms of UL is correlated with a partial return of resting activity to neurons in the vestibular nucleus (VN) on the deafferented side (the "deafferented VN"), and lesions to the deafferented VN prevent compensation; therefore, the regeneration of resting activity within the deafferented VN is believed to have a causal role in vestibular compensation. The biochemical mechanisms responsible for the adaptive neuronal changes within the deafferented VN are poorly understood. Neuropeptide hormone fragments, such as adrenocorticotrophic hormone (ACTH)-4-10, have been shown to accelerate vestibular compensation and can act directly on some VN neurons in vitro. Antagonists for the N-methyl-D-aspartate (NMDA) receptor have been shown to inhibit vestibular compensation if administered early in the compensation process. Biochemical studies in frog indicate marked alterations in the phosphorylation patterns of several proteins during compensation, and the in vitro phosphorylation of some of these proteins is modulated by ACTH-(1-24), calcium (Ca2+), and calmodulin or protein kinase C. It is therefore possible that ACTH fragments and NMDA antagonists (via their effects on NMDA receptor-mediated Ca2+ channels) modulate vestibular compensation through their action on Ca(2+)-dependent pathways within VN neurons. Recent studies have shown that some Ca2+ channel antagonists and the Ca(2+)-dependent enzyme inhibitor calmidazolium chloride facilitate vestibular compensation. How the regulation of Ca2+ may be related to the neuronal changes responsible for vestibular compensation is unclear at present.     

Survival of Trauma-Injured Neurons in Rat Brain by Treatment with Proline-Rich Peptide (PRP-1): An Immunohistochemical Study

The objective of this immunohistochemical research was to reveal the distribution of a proline-rich peptide-1 (PRP-1) in various brain structures of intact and trauma-injured rats and to identify the mechanisms of promotion of neuronal recovery processes following PRP-1 treatment. PRP-1, produced by bovine hypothalamic magnocellular cells and consisting of 15 amino acid residues, is a fragment of neurophysin vasopressin associated glycoprotein isolated from bovine neurohypophysis neurosecretory granules. PRP-1-immunoreactivity (PRP-1-IR) was detected in the brain of intact rats in the neurons of paraventricular (PVN) and supraoptic (SON) nuclei in the hypothalamus, in almost all cell groups in the medulla oblongata, in Purkinje and some cerebellar nuclei cells, and in nerve fibers. At 3 weeks after hemisection of the spinal cord (SC) an asymmetry of PRP-1 localization in the PVN and SON was observed: no PRP-1-IR was exhibited at the affected sides of both nuclei. Daily intramuscular administration of PRP-1 for 3 weeks significantly increased the number of PRP-1-immunoreactive (PRP-1-Ir) varicose nerve fibers, and cells in PVN and SON and in cell groups of the limbic system and brain stem. Tanycytes in the median eminence and covering ependyma also demonstrated strong PRP-1-IR. PRP-1 treatment also activated neuropeptide Y-IR (NPY-IR) in nerve fibers and immunophilin fragment-IR (IphF-IR) in lymphocytes and nerve cells. A strong increase of PRP-1-IR was observed in the PVN and SON of SC-injured rats following the treatment with another PRP (PRP-3). Preliminary physiological data demonstrate that PRP-3 is more "aggressive" in the recovery processes than PRP-1. Based on the findings regarding PRP action on neurons survival, axons regeneration, and the number of IphF-Ir lymphocytes and NPY-Ir nerve fibers, PRP is suggested to act as a neuroprotector, functioning as a putative neurotransmitter and immunomodulator.     

Comparative Study of Structure and Activity of Cytotoxins from Venom of the Cobras Naja oxiana, Naja kaouthia, and Naja haje

Cytotoxins are positively charged polypeptides that constitute about 60% of all proteins in cobra venom; they have a wide spectrum of biological activities. By CD spectroscopy, cytotoxins CT1 and CT2 Naja oxiana, CT3 Naja kaouthia, and CT1 and CT2 Naja haje were shown to have similar secondary structure in an aqueous environment, with dominating beta-sheet structure, and to vary in the twisting angle of the beta-sheet and the conformation of disulfide groups. Using dodecylphosphocholine micelles and liposomes, CT1 and CT2 Naja oxiana were shown to incorporate into lipid structures without changes in the secondary structure of the peptides. The binding of CT1 and CT2 Naja oxiana with liposomes was associated with an increase in the beta-sheet twisting and a sign change of the dihedral angle of one disulfide group. The cytotoxins were considerably different in cytotoxicity and cooperativity of the effect on human promyelocytic leukemia cells HL60, mouse myelomonocytic cells WEHI-3, and human erythroleukemic cells K562. The most toxic CT2 Naja oxiana and CT3 Naja kaouthia possessed low cooperativity of interaction (Hill coefficient h = 0.6-0.8), unlike 10-20-fold less toxic CT1 and CT2 Naja haje (h = 1.2-1.7). CT1 Naja oxiana has an intermediate position on the cytotoxicity scale and is characterized by h = 0.5-0.8. The cytotoxins under study induced necrosis of HL60 cells and failed to activate apoptosis. The differences in cytotoxicity are supposed to be related not with features of the secondary structure of the peptides, but with interactions of side chains of variable amino acid residues with lipids and/or membrane proteins.     

Recording of short-latency vestibular evoked potentials induced by acceleration impulses in experimental animals: current status of the method and its applications

The short-latency vestibular evoked potential (VsEP) induced by angular acceleration impulses (maximal amplitude 30,000 deg/sec², rise time 2–3 msec) was recorded by skin electrodes in intact cats after various surgical and pharmacological procedures. The normal VsEP consists of 5–8 waves, several microvolts in amplitude, during the first 10 msec. The latency of the first wave (P1) is about 2 msec with respect to the start of head acceleration. The first and the second waves (P1 and P2) were shown to originate from the vestibular nerve and nucleus, respectively.The VsEP disappears permanently after bilateral labyrinthectomy, excision of the 8th nerves, or administration of large doses of gentamicin. Temporary disappearance is caused by anoxia induced for a brief period of time or injection of lidocaine (4%) into the vestibular nerve or into the inner ear after contralateral labyrinthectomy.The VsEPs in the intact cat are similar whether clockwise or counterclockwise stimuli are used and are not affected by changing the position of the head. Unilaterally labyrinthectomized animals, however, show asymmetric response whereby excitatory stimulation of any of the intact semicircular canals evokes prominent P1 and P2 waves which are absent with inhibitory stimulation.The rate and input-output intensity functions of the VsEP are described. The threshold of the VsEP was found to be 1000–1500 deg/sec².In addition to the neurogenic waves, 2 other potentials appear occasionally in the response: (1) large-amplitude and longer-duration waves with latencies of 8–20 msec, which are of myogenic origin, and (2) smaller waves with shorter latency which probably represent vestibular microphonics and generator potentials. Extracellular recordings of the responses of single second-order neurons in the vestibular nuclei to the same acceleration impulses confirmed that the kinetic vestibular neurons can respond to these stimuli with a latency as short as 3.5 msec.This method for inducing and recording VsEPs has proved to be a powerful tool for the evaluation of vestibular function in experimental animal models.     

眼镜蛇毒注射液对动物心血管系统神经系统及呼吸系统影响的研究

本文报告眼镜蛇毒注射液对动物的神经系统无不良影响;不影响猫、大鼠的血压;注射三种剂量后对家兔、猫、大鼠三种动物的心电图波形不产生影响,可使心律稍有降低,但在２．５小时后恢复正常;眼镜蛇毒注射液低剂量组对动物呼吸频率无不良影响,中高剂量组槿使呼吸频率销有下降,但在２．５小时后恢复正常。     

Antitumorigenic Effect of Brain Proline Rich Polypeptide-1 in Human Chondrosarcoma

Proline rich polypeptide (PRP-1) produced by neurosecretory cells of the hypothalamus is one of the fragments of neurophysin-vasopressin-associated glycoprotein. The primary structure of the neuropeptide PRP-1 isolated from neurosecretory granules of bovine neurohypophysis. We investigated PRP-1 action on chondrosarcoma, the second most common malignancy in bone, which primarily affects the cartilage cells. This deadly disease does not have any effective treatment. Earlier we demonstrated MYC oncogene inactivating effect by 1 μg/ml concentration brain PRP-1 In the present study we observed reduced viable sarcoma JJ012 cell numbers in comparison with control (89% growth inhibition) when treated with low concentrations of PRP-1 (0.5–1 μg/ml). Higher concentrations did not exhibit inhibitory effect. We assume that PRP-1 in low concentration impedes cell cycle progression. The fact that low concentrations of PRP-1 abolished Myc activity prompts to think that the antitumorigenic effect of PRP-1 in low concentrations is mediated through oncogene inactivation.     

Neuroprotective Action of Hypothalamic Peptide PRP-1 at Various Time Survivals Following Spinal Cord Hemisection

The purpose of the present study was to evaluate the neuroprotective action of proline-rich peptide-1 (PRP-1) produced by hypothalamic nuclei cells (nuclei paraventricularis and supraopticus) following lateral hemisection of spinal cord (SC). The dynamics of rehabilitative shifts were investigated at various periods of postoperative survival (1–2, 3, and 4 weeks), both with administration of PRP-1 and without it (control). We registered evoked spike flow activity in both interneurons and motoneurons of the same segment of transected and symmetric intact sides of SC and below it on the stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius) and extensor (n. peroneus communis) nerves. In the control group (administration of 0.9% saline as placebo), no significant decrease of post-stimulus activity of neurons was observed on the transected side by the 2nd week. This activity strongly decreased by week 3 postaxotomy, with some increase on the intact side, possibly of compensatory origin. No shifts occurred by the 4th week. Regardless of the period of administration, PRP-1 increased neuronal activity on the transected side, with the same activation levels on both SC sides. These data were confirmed by histochemical investigation. PRP-1 administration, both daily and every other day, for a period of 2–3 weeks led to prevention of scar formation and promotion of the re-growth of white matter nerve fibers in the damaged area. It also resulted in prevention of neuroglial elements degeneration and reduction in gliosis expression in the lesion supporting neuronal survival. Thus, PRP-1 achieved protection against “tissue stress”, which was also confirmed by the registration of activity on the level of transection and restoration of the motor activity on the injured side. The obtained data propose the possibility of PRP-1 application in clinical practice for prevention of neurodegeneration of traumatic origin.     

Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)