Reaction In Rats Research Articles

Effects of Experimental Increases and Decreases in Thyroxine Levels on the Extent of Cataleptic Freezing Reactions in Rats

Numerous clinical observations have provided evidence for a tight connection between impairments in the functions of the hypothalamo-hypophyseal-thyroid system and nervous and mental disorders. The aim of the present work was to compare the effects of experimental decreases and increases in blood thyroxine levels on the extents of two types of pathological freezing reaction in male Wistar rats--spontaneous catalepsy and catalepsy evoked by pinches at the nape of the neck (pinch-induced catalepsy). Chronic administration of the thyroxine synthesis inhibitor propylthiouracil (5 mg/kg/day for 28 days) significantly decreased the blood hormone level and sharply increased the proportion of animals showing spontaneous catalepsy and the immobility time, but had no effect on the extent of pinch-induced catalepsy. At the same time, chronic administration of thyroxine (0.1 mg/kg/day for 28 days), which produced significant increases in blood hormone levels, had no effect on the extent of spontaneous catalepsy but significantly increased the proportion of animals showing pinch-induced catalepsy and the duration of this type of catalepsy. It is concluded that both insufficiency and excess of thyroid hormones have cataleptogenic actions, but enhance different types of catalepsy.

Antioxidant effect of squeezed juice from black radish (Raphanus sativus L. var niger) in alimentary hyperlipidaemia in rats

Black radish (Raphanus sativus L. var. niger) root has been used in folk medicine since antiquity as a natural drug for the stimulation of bile function. According to in vitro studies the squeezed juice from black radish root exhibited significant antioxidant properties. In the present study, the beneficial effect of the black radish juice on some free radical reactions in rats fed with a diet rich in lipids (20% sunflower oil, 2% cholesterol, 0.5% cholic acid in normal chow) was examined. Thiobarbituric acid reactive substances and conjugated diene concentrations were significantly higher, while the antioxidant enzyme activities and the free radical scavenging capacity were lower in hyperlipidaemic rats compared with normal controls. Supplementation of the lipid-rich diet with black radish juice resulted in a significant improvement of the parameters mentioned above. Although the exact mechanism of the biologically active compounds in black radish on the lipid metabolism and lipid peroxidation is not clear yet, a beneficial effect of the drug was evident in alimentary hyperlipidaemia.

Amphetamine-induced aggression is enhanced in rats pre-treated with the anabolic androgenic steroid nandrolone decanoate

Aggression is one of the most commonly reported psychiatric side effects among anabolic–androgenic steroids (AAS) users. Furthermore, anecdotal stories say the aggression is even more profound when a current, or former, AAS-user consumes other drugs of abuse such as amphetamine and alcohol. In the present study, we examined the effect of amphetamine on defensive reactivity and defensive aggression in Sprague–Dawley rats after chronic AAS treatment (daily intramuscular [i.m.] injections with 15 mg/kg nandrolone decanoate [ND] for 14 days). Defensive reactions in rodents occur in response to a real threat, but also to perceived provocation, for example, elicited by innocuous stimuli as reaction towards the experimenter. The defensive reactivity and aggression test employed in this study evaluates each rat's reaction towards four different stimuli (I: approach of a rod; II: startle to an air puff; III: poking with a rod at the flanks, and IV: capturing with a gloved hand) at two different occasions. Immediately following the ND treatment period, no change in the defensive response was found. Nevertheless, an amphetamine challenge given 3 weeks after the last ND or vehicle injection induced a marked increased defensive aggressive response in the ND, compared to vehicle-pre-treated rats. Both ND- and vehicle-pre-treated rats receiving amphetamine were found to be more aggressive than comparable groups receiving a saline injection. It can be concluded that pre-treatment with ND modulates the behavioral response to amphetamine and induces long lasting changes in the behavioral response.

Modification of sensitization methods can induce allergic inflammation in the lungs of allergy-resistant Sprague Dawley rats

RATIONALE: The development of severe allergic reactions in rats is strain-specific. Sprague Dawley (SD) rats are normally quite insensitive to allergens. The aim of this study was to develop modified methods of sensitization for inducing allergic airway reactions in SD rats.

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.

Effects of dimephosphone, xydiphone, and ionol on the content and activities of rat liver cytochromes P-450 during long-term treatment with phenobarbital

Effects of dimephosphone, xydiphone, and ionol administered in parallel with phenobarbital on the content of cytochromes P-450 in rat liver and on the rate of C-hydroxylation of diazepam, haloperidol, and prednisolone by rat liver microsomal enzymes were studied in vitro. Dimephosphone, xydiphone, and ionol exhibited similar inductive effects on C-hydroxylation reactions in the CYP P-450 system during treatment with phenobarbital. Xydiphone and ionol in a dose of 1 mmol/kg canceled phenobarbital-induced increase in P-450 cytochrome content in rat liver. Sex-dependent cytochromes P-450 are involved in the prednisolone and haloperidol C-hydroxylation reactions in rats.

Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment.

The present investigation was undertaken in order to evaluate the contributions of ATP synthesis and proton leak reactions to the rate of active respiration of liver mitochondria, which is altered following dexamethasone treatment (1.5 mg/kg per day for 5 days). We applied top-down metabolic control analysis and its extension, elasticity analysis, to gain insight into the mechanisms of glucocorticoid regulation of mitochondrial bioenergetics. Liver mitochondria were isolated from dexamethasone-treated, pair-fed and control rats when in a fed or overnight fasted state. Injection of dexamethasone for 5 days resulted in an increase in the fraction of the proton cycle of phosphorylating liver mitochondria, which was associated with a decrease in the efficiency of the mitochondrial oxidative phosphorylation process in liver. This increase in proton leak activity occurred with little change in the mitochondrial membrane potential, despite a significant decrease in the rate of oxidative phosphorylation. Regulation analysis indicates that mitochondrial membrane potential homoeostasis is achieved by equal inhibition of the mitochondrial substrate oxidation and phosphorylation reactions in rats given dexamethasone. Our results also suggest that active liver mitochondria from dexamethasone-treated rats are capable of maintaining phosphorylation flux for cellular purposes, despite an increase in the energetic cost of mitochondrial ATP production due to increased basal proton permeability of the inner membrane. They also provide a complete description of the effects of dexamethasone treatment on liver mitochondrial bioenergetics.

Comparison of the effects of entorhinal and retrosplenial cortical lesions on habituation, reaction to spatial and non-spatial changes during object exploration in the rat

This study was aimed at comparing the effects of damage to the entorhinal cortex and retrosplenial cortex on exploration and reaction-to-change in rats. Following habituation to a configuration of objects, a familiar object was displaced therefore producing a spatial change. A non-spatial change was made by substituting a familiar object by a novel object. Both entorhinal cortex lesions and retrosplenial cortex lesions elicited a deficit in the rat's reaction to a spatial change. In addition, rats with entorhinal lesions showed hypoactive object exploration and exhibited a mild deficit in reaction to a non-spatial change. This may reflect the importance of temporal cortical input in object recognition. Overall, these results suggest that the entorhinal cortex and the retrosplenial cortex contribute to the processing of the geometric properties of the environment and have thus close functional links.

Bipolar Manifestation of Cataleptic Reactions in Rats

Selection of GC rats for the predisposition to cataleptic freezing has increased not only the frequency, intensity, and duration of freezing, but also the proportion of irritable or "nervous" rats with enhanced anxiety, defensive behavior with vocalization, jerky running, and jumpiness. An increased amplitude of the startle reflex is a correlate of this "nervousness." The results of the comparison of some behavioral characters in the nervous and freezing GC rats, as well as in F1 and F2 offspring from homogeneous crosses between nervous and freezing GC rats suggest that cataleptic freezing and nervousness are two poles of the same bipolar catatonic reaction. They have a common mechanism, with the alternative or preferential expression of one particular form of the reaction is determined by the external and internal environments or the set of modifier genes in the given individual.

Comparison of the effects of entorhinal and retrosplenial cortical lesions on habituation, reaction to spatial and non-spatial changes during object exploration in the rat

This study was aimed at comparing the effects of damage to the entorhinal cortex and retrosplenial cortex on exploration and reaction-to-change in rats. Following habituation to a configuration of objects, a familiar object was displaced therefore producing a spatial change. A non-spatial change was made by substituting a familiar object by a novel object. Both entorhinal cortex lesions and retrosplenial cortex lesions elicited a deficit in the rat's reaction to a spatial change. In addition, rats with entorhinal lesions showed hypoactive object exploration and exhibited a mild deficit in reaction to a non-spatial change. This may reflect the importance of temporal cortical input in object recognition. Overall, these results suggest that the entorhinal cortex and the retrosplenial cortex contribute to the processing of the geometric properties of the environment and have thus close functional links.

Neural correlates of cat odor-induced anxiety in rats: region-specific effects of the benzodiazepine midazolam.

Cat odor elicits a profound defensive reaction in rats that is reduced by benzodiazepine drugs. The neural correlates of this phenomenon were investigated here using Fos immunohistochemistry. Rats received either midazolam (0.75 mg/kg, s.c.) or vehicle and were exposed to pieces of a collar that had been worn by a domestic cat or an unworn (dummy) collar. Cat odor caused midazolam-sensitive defensive behavioral responses, including avoidance of collar contact, inhibition of grooming, and prolonged rearing. Cat odor exposure induced Fos expression in the posterior accessory olfactory bulb (glomerular, mitral, and granule cell layers), with granule cell layer activation attenuated by midazolam. High basal Fos expression, and some cat odor-associated Fos expression, was evident in the main olfactory bulb (glomerular cell layer), and midazolam exerted a strong inhibitory effect in this region. Midazolam inhibited Fos expression in key limbic regions involved in pheromone transduction (medial amygdala and bed nucleus of the stria terminalis) and defensive behavior (prelimbic cortex, lateral septum, lateral and medial preoptic areas, and dorsal premammillary nucleus). However, midazolam failed to affect cat odor-related Fos expression in a range of key defense-related sites, including the ventromedial hypothalamic nucleus, paraventricular nucleus of the hypothalamus, periaqueductal gray, and cuneiform nucleus. These results indicate that midazolam exerts a region-specific effect on the neural substrates activated by predator odor, with effects in the lateral septum and dorsal premammillary nucleus likely to be of major importance. These findings also suggest the intriguing hypothesis that cat odor is processed by rats as a "pheromone-like" stimulus.

Characteristics of the actions of neurotensin on motor reactions in rats in response to positive and negative conditioned signals.

This study addressed the effects of microinjections of neurotensin into the caudate nucleus and substantia nigra on the performance of motor reactions in response to positive and negative conditioned signals, as well as the post-effects of microinjections in subsequent experiments. Neurotensin had positive effects on the extinction of non-reinforced motor reactions. Neurotensin had no effect on the number of motor responses to the non-reinforced signal, though the number decreased in subsequent experiments. There was an increase in the latent period of responses as compared with controls. The effect of neurotensin at the level of the caudate nucleus was more marked than that at the level of the substantia nigra. Neurotensin microinjections had no marked effect on performance of conditioned responses to positive signals. The behavioral effects of neurotensin are associated with normalization of the interactions of the brain's monoaminergic systems. It is suggested that the positive actions of neurotensin on extinction of motor responses to negative signals result from the formation of a contextual conditioned emotional state in the animals, this facilitating optimization of conditioned reflex activity.

Effect of Nicotine-Induced Corticosterone Elevation on Nitric Oxide Production in the Passive Skin Arthus Reaction in Rats

To elucidate the anti-inflammatory action of nicotine-induced corticosterone elevation on the passive skin Arthus reaction (PSAR), we investigated the inflammatory process in the PSAR. The polymorphonuclear leukocyte (PMNs) infiltration was observed just before as well as after elicitation by measuring extractable myeloperoxidase. The plasma exudation was significantly inhibited by anti-rat tumor necrosis factor (TNF)-α antibody (5 μg/site, i.d.) at the time of sensitization or by superoxide dismutase (52500 units/kg, i.p.) 1 h before elicitation or NG-nitro-L-arginine-methyl ester (100 mg/kg, i.v.) just at elicitation. Pretreatment with a single injection of nicotine (0.8 mg/kg, i.p.) 30 min before elicitation suppressed the plasma exudation but not the PMNs infiltration. This nicotine-induced decreasing effect was abolished in animals supplemented with L-arginine (300 mg/kg, i.v.) just at elicitation. The production of nitric oxide (NO) in peritoneal PMNs derived from an animal injected peritoneally with oyster glycogen was significantly suppressed by pretreatment with nicotine (0.8 mg/kg, i.v.) 30 min prior to harvesting. This inhibitory action of nicotine was abolished in animals pretreated with mifepristone (30 mg/kg, s.c.), a glucocorticoid receptor antagonist. These findings indicate that a single systematic administration of nicotine may attenuate the plasma exudation in the PSAR by suppressing the production of NO in the PMNs primed with TNF-α via nicotine-induced endogenous glucocorticoid.

Respiratory Reactions in Rats to Microinjections of Bombesin into the Region of the Nucleus Tractus Solitarius

In experiments on 35 mongrel albino rats, we studied the effects of a neuropeptide, bombesin (0.2 μl, concentrations from 10-13 to 10-4), which was injected into the nucleus tractus solitarius, on the pattern of respiration and on the electrical activity of the main inspiratory muscles. The local influence of bombesin on this region of the respiratory center led to the expressed intensification of respiration. The respiratory volume and the amplitude of respiratory EMG bursts (oscillatory volleys in the diaphragmatic and external intercostal muscles), as well as the integral intensity of pulmonary ventilation, increased. The maximum deviations of these indices developed under the influence of the peptide in the intermediate concentrations (10-10 to 10-7 M). The observed reactions were characterized by short latencies, rapid development (2 to 5 min long), and relatively short duration. The data obtained are indicative of the possibility of direct involvement of the tested neuropeptide (bombesin) in the control of respiration and confirm concepts on the important role of the dorsal structures of the respiratory center in realization of respiratory effects of neuropeptides.

Sequential changes of connexin32 and connexin26 in ischemia-reperfusion of the liver in rats

Serial changes in expression of hepatic gap junction components, connexin32 and connexin26 expressions during ischemia (60 min)-reperfusion injury of the liver were evaluated by immunofluorescence staining and reverse transcription-polymerase chain reaction in rats. Hepatic tissue calcium content and liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), were also examined. Connexin expressions were down-regulated during ischemia and steeply increased during the early reperfusion period. This upsurge in connexin was coincided with the augmentation in tissue calcium content level. And the mRNA levels of connexin changed in parallel with the connexin protein level until 60 min after reperfusion. Since it is known that the changes in intracellular Ca 2+ concentration controls the intercellular communication via gap junction, these findings suggest the possibility that gap junction may play a definitive role in reperfusion injury of the liver. Further studies may be necessary to clarify the exact role of connexins in hepatic ischemia-reperfusion injury.

Myotoxicity induced by an acidic Asp-49 phospholipase A 2 isolated from Lachesis muta snake venom : Comparison with lysophosphatidylcholine

In a previous report we showed that Lachesis muta crude venom displays potent indirect hemolytic activity and myotoxicity when injected into mice. Then, a phospholipase A 2 (PLA 2) (LM-PLA 2-I) responsible for these activities was isolated. More recently, a catalytically active isoenzyme (LM-PLA 2-II) with molecular mass of 18 kDa and isoeletric point at pH 5.4 was isolated from the same snake venom. LM-PLA 2-II inhibited ADP- and collagen-induced platelet aggregation as well as induced a potent paw edema reaction in rats. Here we show that LM-PLA 2-II induced myotoxic effects both in vitro characterized by an increase on the rate of creatine kinase (CK) release from isolated mice extensor digitorum longus (EDL) muscles and in vivo by increasing plasma CK activity of injected mice. Histological analysis showed an intense damage in muscle cells injected with LM-PLA 2-II. It was also shown that exogenous lysophosphatidylcholine (lyso-pc) behaved as a typical myotoxin damaging muscle cells, producing myonecrosis characterized by local infiltration of inflammatory cells similarly to that observed for LM-PLA 2-II. Hemorrhage and lethal effects were not observed neither with LM-PLA 2-II nor lyso-pc. As previously observed for other biological activities, pretreatment of LM-PLA 2-II with p-bromophenacyl bromide ( p-BPB) or acetic anhydride abolished all the enzyme’s actions. The data confirms that biological activities displayed by LM-PLA 2-II, including the myotoxic effects reported here, are all dependent on its enzymatic activity where the product formed (lyso-pc) may play an important function on such myotoxicity.

The 5-HT1A agonist 8-OH-DPAT dose-dependently interferes with the establishment and the expression of lithium-induced conditioned rejection reactions in rats.

The present experiments evaluated the potential of the 5-HT(1A )agonist, 8-OH-DPAT (DPAT), which reduces serotonin availability, to interfere with both the establishment and with the expression of lithium-induced conditioned rejection reactions (experiment 1) and lithium-induced taste avoidance (experiment 2). OBJECTIVES. To determine the effect of reduced serotonin availability on conditioned rejection reactions, a rat model of nausea. Rats were injected with 8-OH-DPAT [at doses of 0.0 (saline), 0.01 or 0.1 mg/kg, SC] 30 min prior to exposure to 0.1% saccharin solution by intra-oral infusion (experiment 1) or by bottle presentation (experiment 2). Immediately following saccharin exposure, rats were injected with 20 ml/kg lithium chloride (0.15 M) or 20 ml/kg saline solution. On each of three test trials, rats were injected with DPAT [0.0 (saline), 0.01 and 0.1 mg/kg, SC; counterbalanced order], 30 min prior to exposure to saccharin solution by intra-oral infusion (experiment 1) or by a two-bottle test (experiment 2: saccharin and water). DPAT interfered with both the establishment (at a dose of 0.1 mg/kg, SC) and with the expression (at doses of 0.01 and 0.1 mg/kg, SC) of lithium-induced conditioned rejection reactions; however, DPAT did not modulate taste avoidance in a consumption test. These results indicate that conditioned rejection reactions, but not taste avoidance, can be attenuated by the anti-emetic agent, 8-OH-DPAT.

Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea.

Marijuana has been reported to suppress nausea produced by chemotherapy treatment in human cancer patients. Although there is abundant evidence that cannabinoid agonists attenuate vomiting in emetic species, there has been little experimental evidence of their anti-nausea potential. Considerable evidence suggests that conditioned rejection reactions in rats reflect nausea. The present experiments evaluated the potential of low doses of the cannabinoid agonists, delta-9-tetrahydrocannabinol (THC; 0.5 mg/kg, i.p.), and HU-210 (0.001 mg/kg and 0.01 mg/kg, i.p.), and the CB(1) antagonist SR-141716A in modulating the establishment and the expression of lithium-induced conditioned rejection reactions in rats. To evaluate the effect of cannabinoids on conditioned rejection reactions, a rat model of nausea. In experiments 1 and 2, respectively, rats were injected with cannabinoid agonists, THC (0.5 mg/kg, i.p.) and HU-210 (0.001, 0.005 or 0.01 mg/kg), 30 min prior to exposure to 0.1% saccharin solution by intraoral infusion. Immediately following saccharin exposure, they were injected with 20 ml/kg 0.15 M lithium chloride or saline. On each of two test trials, the rats were injected with the cannabinoid or vehicle 30 min prior to exposure to saccharin. In experiment 3, rats were injected with the CB(1) antagonist, SR-141716A (2.5 mg/kg) or a combination of SR-141716A and HU-210 (0.01 mg/kg) 30 min prior to an infusion of saccharin followed by injection of lithium or saline. They were given a single drug-free test trial. Experiment 4 replicated and extended the findings of experiment 3. delta-9-THC and HU-210 interfered with the establishment and the expression of lithium-induced conditioned rejection reactions. The suppressive effect of HU-210 on rejection reactions was reversed by pretreatment with SR-141716A. Administration of SR-141716A prior to conditioning potentiated lithium-induced conditioned rejection reactions. These results indicate that the establishment and the expression of lithium-induced conditioned rejection reactions are suppressed by pretreatment with cannabinoid agents. These effects appear to be mediated by their action on the CB(1) receptor, because they are reversed by pretreatment with SR-141716A. Finally, our results suggest that endogenous cannabinoids play a role in modulation of nausea, because the antagonist potentiated lithium-induced nausea.

Effect of Glutathione Depletion and Hydrophilic Bile Acids on Hepatic Acute Phase Reaction in Rats with Extrahepatic Cholestasis

Background: Extrahepatic cholestasis by biliary obstruction induces an acute phase reaction in the liver. It is a complex process involving cytokines, hormones and growth factors. To determine whether the regulation of acute phase proteins (APP) in cholestasis depends on glutathione (GSH), the effect of buthionine sulfoximine-induced (BSO-induced) GSH depletion on the expression of various APP was studied. In addition, we determined the influence of hepatoprotective bile acids on hepatic APP and underlying cytokine events. Methods: Liver samples of bile-duct-ligated or sham-operated rats were examined. mRNA expression was quantified by densitometric analysis of Northern blots. Results: Expression of APP increased 2-5-fold in bile-duct-ligated rats as compared to sham-operated controls. This acute phase reaction remained similar independently of whether cholestasis occurred for 5 days or 3 weeks. In contrast to ! 2-macroglobulin and tissue inhibitor of metalloproteinases-1 (TIMP-1), mRNA levels of both # -fibrinogen and haptoglobin were significantly up-regulated after GSH depletion by BSO in cholestasis. Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated ! 2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of # -fibrinogen and haptoglobin. Cholestasis leads to an increased APP expression accompanied by an increased expression of inflammatory cytokines (IL-6, TNF- ! ). After feeding of hydrophilic bile acids, increases in inflammatory cytokines were abrogated. Conclusions: We show that GSH is involved in the acute phase reaction during obstructive cholestasis. In addition, bile acids might selectively ameliorate the acute phase response by reducing expression of the APP not affected by GSH depletion ( ! 2-macroglobulin and TIMP-1).

Effects of orally administered olopatadine hydrochloride on the ocular allergic reaction in rats

Olopatadine hydrochloride is an antiallergic agent with histamine H 1 receptor antagonistic action. We investigated the effects of olopatadine on passive anaphylaxis reaction- and compound 48/80-induced conjunctivitis in rats. Allergic conjunctivitis was induced in rats passively sensitized by injection of rat anti-ovalbumin (anti-OVA) serum into the upper subconjunctiva of the right eye, followed by intravenous administration of the antigen and Evans blue dye. After 30 min, the amount of dye leaking into the conjunctiva was measured. Non-allergic conjunctivitis was induced in rats by injection of compound 48/80. Olopatadine or other reference compounds were orally given 1 h before the challenge. The amount of dye leaking into the conjunctiva following passive anaphylaxis was significantly inhibited by oral administration of 0.01-1 mg/kg olopatadine and the ID 50 value was 0.093 mg/kg. In the control group, pathological examination revealed edema and lymphocyte infiltration in the conjunctiva and the palpebral skin. Olopatadine, at 0.03 and 0.3 mg/kg, reduced the grade of these pathological findings. The other antiallergic drugs (1 mg/kg loratadine, 0.3 mg/kg epinastine, 0.3 mg/kg cetiridine, 1 mg/kg ebastine, 30 mg/kg fexofenadine and 3 mg/kg chlorpheniramine), when administered orally, inhibited the passive anaphylaxis reaction-induced vascular hyperpermeability of the conjunctiva, as was the case with olopatadine hydrochloride. Subconjunctival administration of compound 48/80 induced vascular hyperpermeability, which is presumably mediated by histamine release. Oral administration of 0.1 and 1 mg/kg olopatadine significantly inhibited the amount of dye leakage. Orally administered olopatadine is expected to improve allergic conjunctivitis.