Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

BACKGROUND: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. AIMS: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). METHODS: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. RESULTS: Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. CONCLUSION: In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients.

Do pediatric medicines induce topographic changes in dental enamel?

The purpose of the present study was to evaluate the effect of common pediatric liquid medicines on surface roughness and tooth structure loss and to evaluate the pH values of these medicines at room and cold temperatures in vitro. Eighty-four bovine enamel blocks were divided into seven groups (n = 12): G1-Alivium®, G2-Novalgina®, G3-Betamox®, G4-Clavulin®, G5-Claritin®, G6-Polaramine® and G7-Milli-Q water (negative control). The pH was determined and the samples were immersed in each treatment 3x/day for 5 min. 3D non-contact profilometry was used to determine surface roughness (linear Ra, volumetric Sa) and the Gap formed between treated and control areas in each block. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were also performed. The majority of liquid medicines had pH ≤ 5.50. G1, G4, and G5 showed alterations in Ra when compared with G7 (p < 0.05). According to Sa and Gap results, only G5 was different from G7 (p < 0.05). Alteration in surface was more evident in G5 SEM images. EDS revealed high concentrations of carbon, oxygen, phosphorus, and calcium in all tested groups. Despite the low pH values of all evaluated medicines, only Alivium®, Clavulin®, and Claritin® increased linear surface roughness, and only Claritin® demonstrated the in vitro capacity to produce significant tooth structure loss.

Do pediatric medicines induce topographic changes in dental enamel?

Abstract The purpose of the present study was to evaluate the effect of common pediatric liquid medicines on surface roughness and tooth structure loss and to evaluate the pH values of these medicines at room and cold temperatures in vitro. Eighty-four bovine enamel blocks were divided into seven groups (n = 12): G1-Alivium®, G2-Novalgina®, G3-Betamox®, G4-Clavulin®, G5-Claritin®, G6-Polaramine® and G7-Milli-Q water (negative control). The pH was determined and the samples were immersed in each treatment 3x/day for 5 min. 3D non-contact profilometry was used to determine surface roughness (linear Ra, volumetric Sa) and the Gap formed between treated and control areas in each block. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were also performed. The majority of liquid medicines had pH ≤ 5.50. G1, G4, and G5 showed alterations in Ra when compared with G7 (p < 0.05). According to Sa and Gap results, only G5 was different from G7 (p < 0.05). Alteration in surface was more evident in G5 SEM images. EDS revealed high concentrations of carbon, oxygen, phosphorus, and calcium in all tested groups. Despite the low pH values of all evaluated medicines, only Alivium®, Clavulin®, and Claritin® increased linear surface roughness, and only Claritin® demonstrated the in vitro capacity to produce significant tooth structure loss.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice.

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing.

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

l-histidine induces state-dependent memory deficit in mice mediated by H(1) receptor.

This study investigated the role of H(1) receptor in the state-dependent memory deficit induced by l-histidine (LH) in mice using Trial 1/2 protocol in the elevated plus-maze (EPM). The test was performed for two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before both trials, mice received a combined injection i.p. of saline+saline (SAL/SAL), 500 mg/kg L-histidine+saline (LH/SAL), 500 mg/kg L-histidine+16 mg/kg chlorpheniramine (LH/CPA) or saline+16 mg/kg chlorpheniramine (SAL/CPA). The trials were performed in the EPM 10 min after the last injection. Each animal was placed in the center of the maze facing the open arm and had five minutes to explore it. On both days, test sessions were videotaped. The behavioral measures were scored from videotape. Data were analyzed based on Analysis of Variance (ANOVA) and the Fisher's LSD test. The data showed no effects on anxiety since there was no difference between the SAL/SAL and the other groups in Trial 1, respectively, open arm entries (OAE), open arm time (OAT) and their percentages (%OAE and %OAT). During Trial 2, OAE, OAT, %OAE and %OAT were reduced in mice treated with SAL/SAL, LH/CPA and SAL/CPA, while the group LH/SAL did not show any difference in these measures. No significant changes were observed in enclosed arm entries (EAE), an EPM index of general exploratory activity. Thus, it can be suggested that LH induces emotional memory deficit and the treatment with chlorpheniramine was able to revert this effect, suggesting this action of LH was mediated by the H(1) receptor.

Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study.

In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 microm column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation.

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean +/- SEM) of the A-SAL (586.3 +/- 13.6) and A-CPA (600 +/- 0) groups were significantly longer than those of the S-SAL (226.14 +/- 61.15) and S-CPA (356.33 +/- 68.8) groups. At T8, the latencies of the A-CPA group (510.11 +/- 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 +/- 78.32; S-CPA = 191.58 +/- 73.03; S-SAL = 90.28 +/- 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.

Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.

Chlorpheniramine facilitates inhibitory avoidance in teleosts submitted to telencephalic ablation.

The present study investigated the involvement of H(1) histaminegic receptor on the acquisition of inhibitory avoidance in Carassius auratus submitted to telencephalic ablation. The fish were submitted to telencephalic ablation 5 days before the experiment. The inhibitory avoidance procedure included 1 day for habituation, 3 days for training composed of 3 trials each (1st day: T1, T2, T3; 2nd day: 2T1, 2T2, 2T3; 3rd day: 3T1, 3T2, 3T3) and 1 day for test. On training days, the fish were placed in a white compartment, after 30 s the door was opened. When the fish crossed to a black compartment, a weight was dropped (aversive stimuli). Immediately after the third trial, on training days, the fish received, intraperitoneally, one of the pharmacological treatments (saline (N = 20), 8 (N = 12) or 16 (N = 13) microg/g chlorpheniramine, CPA). On the test day, the time to cross to the black compartment was determined. The latency of the saline group increased significantly only on the 3rd trial of the 2nd training day (mean +/- SEM, T1 (50.40 +/- 11.69), 2T3 (226.05 +/- 25.01); ANOVA: P = 0.0249, Dunn test: P < 0.05). The group that received 8 microg/g CPA showed increased latencies from the 2nd training day until the test day (T1 (53.08 +/- 17.17), 2T2 (197.75 +/- 35.02), test (220.08 +/- 30.98); ANOVA: P = 0.0022, Dunn test: P < 0.05)). These results indicate that CPA had a facilitating effect on memory. We suggest that the fish submitted to telencephalic ablation were able to learn due to the local circuits of the mesencephalon and/or diencephalon and that CPA interferes in these circuits, probably due an anxiolytic-like effect.

Chlorpheniramine facilitates inhibitory avoidance in teleosts submitted to telencephalic ablation

The present study investigated the involvement of H(1) histaminegic receptor on the acquisition of inhibitory avoidance in Carassius auratus submitted to telencephalic ablation. The fish were submitted to telencephalic ablation 5 days before the experiment. The inhibitory avoidance procedure included 1 day for habituation, 3 days for training composed of 3 trials each (1st day: T1, T2, T3; 2nd day: 2T1, 2T2, 2T3; 3rd day: 3T1, 3T2, 3T3) and 1 day for test. On training days, the fish were placed in a white compartment, after 30 s the door was opened. When the fish crossed to a black compartment, a weight was dropped (aversive stimuli). Immediately after the third trial, on training days, the fish received, intraperitoneally, one of the pharmacological treatments (saline (N = 20), 8 (N = 12) or 16 (N = 13) µg/g chlorpheniramine, CPA). On the test day, the time to cross to the black compartment was determined. The latency of the saline group increased significantly only on the 3rd trial of the 2nd training day (mean ± SEM, T1 (50.40 ± 11.69), 2T3 (226.05 ± 25.01); ANOVA: P = 0.0249, Dunn test: P < 0.05). The group that received 8 µg/g CPA showed increased latencies from the 2nd training day until the test day (T1 (53.08 ± 17.17), 2T2 (197.75 ± 35.02), test (220.08 ± 30.98); ANOVA: P = 0.0022, Dunn test: P < 0.05)). These results indicate that CPA had a facilitating effect on memory. We suggest that the fish submitted to telencephalic ablation were able to learn due to the local circuits of the mesencephalon and/or diencephalon and that CPA interferes in these circuits, probably due an anxiolytic-like effect.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish.

This work investigated the effect of the H1 receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental trials were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (maximum period). Time to find food was analysed in seconds. Animals were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group maintained the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animals and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish

This work investigated the effect of the Hj receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental triáis were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (máximum period). Time to find food was analysed in seconds. Animáis were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group mainteined the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animáis and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Involvement of the histaminergic system on appetitive learning and its interaction with haloperidol in goldfish.

This study investigated the actions of the histaminergic system on appetitive learning and memory, and its interaction with the dopaminergic system in goldfish. It consisted of nine sessions, in which fish were tested in a four-arm tank. On day 1, the animals were habituated for 10 min. On day 2, they were placed in one arm and had to find food at the left or the right arm. Time to begin feeding was recorded, and the procedure repeated for more 3 days (training phase). On training day 4, seven groups were injected with saline, seven with haloperidol (2.0 mg/kg) and one with DMSO solution before training and after feeding, three groups received saline, six chlorpheniramine (CPA) (1.0, 4.0 and 8.0 mg/kg), and six l-histidine (LH) (25, 50 and 100 mg/kg). Saline groups were considered as control of CPA and LH treated groups and DMSO as control of haloperidol. A non-injected group was also included. Testing occurred after 24 h. A reversal procedure was conducted 24h after testing and repeated for 3 days. The groups receiving CPA at 1.0 and 8.0 mg/kg and LH at 25, 50 and 100 mg/kg differed between Test and Reversal day 1. Pre-treatment with haloperidol plus 8.0 mg/kg of CPA and 25 and 50 mg/kg of LH reverted the treatment effect. However, in the groups treated with 1.0 mg/kg of CPA and 100 mg/kg of LH, the difference remained. This study confirmed the interaction between the histaminergic and the dopaminergic systems on memory process in goldfish.

Anxiolytic-like effect of chlorpheniramine in inhibitory avoidance in goldfish submitted to telencephalic ablation.

The aim of the present study was to verify the consequences of telencephalic ablation on the learning of inhibitory avoidance and anxiety in goldfish. The animals were submitted to telencephalic ablation or sham operations five days prior to the experimental procedure. The inhibitory avoidance procedure was performed in 3 days using a rectangular aquarium divided into two compartments (black and white) with a central door. On the first day, the animals were habituated for 10 min. On the second and third days, they were injected with saline (SAL), 16 mg/kg Chlorpheniramine (CPA), 40% Propylene glycol (PPG) or 1 mg/kg Diazepam (DZP) twenty minutes before training. Then the animals were placed in the white compartment, the central door was opened and the time spent for crossing between compartments was recorded. After the fish crossed the line between the compartments a 45-g weight was dropped. This procedure was performed three times in a row. The groups submitted or not to telencephalic ablation and treated with SAL presented a difference between training sessions; however, the groups treated with CPA, PPG or DZP did not show any differences between them. These results suggest that the treatment with CPA, PPG or DZP impaired the acquisition of inhibitory avoidance conditioning in animals regardless of telecenphalic ablation. In conclusion, telencephalic ablation does not disrupt the animals' capacity to learn the inhibitory avoidance task, and based on the fact that CPA showed similar effects to those of DZP on the animals submitted or not to telencephalic ablation, we suggest that the CPA presents an anxiolytic-like effect mediated by the diencephalon in goldfish.

Effects of Chlorpheniramine and L-histidine on vestibular compensation in goldfish, Carassius auratus.

Histamine is thought to be involved in the recovery of vestibular function after damage to the vestibular receptors of the inner ear. This study evaluated the effects of post-operative treatment using Chlorpheniramine (H1 histamine antagonist) and L-histidine, (a histaminergic precursor), after hemilabyrinthectomy in goldfish. In this lesion model, the unilateral removal of the labyrinth induces a transient postural imbalance in response to light. After the lesion, the animals were injected intraperitoneally, during 12 consecutive days, with Chlorpheniramine, L-histidine and saline. All the substances were administered in a volume of 1 ml/kg body weight. Another group, which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. Chlorpheniramine accelerated the functional recovery when compared with that of the saline group. These data suggest that the inhibition of the histaminergic system facilitates the functional recovery in goldfish.

Haloperidol and chlorpheniramine interaction in inhibitory avoidance in goldfish.

The purpose of this study was to investigate a possible interaction between histaminergic and dopaminergic systems in learning and memory processes, in an inhibitory avoidance test in goldfish. Haloperidol, a dopaminergic antagonist, was administrated pre-training and the chlorpheniramine (CPA), a histaminergic antagonist, post-training. The inhibitory avoidance procedure was performed in 3 days, using a rectangular aquarium divided into two compartments (black and white), with a central door. On the first day, the animals were habituated for 10 min. On the second day, they were injected with 2 mg/kg of haloperidol or dimethyl sulfoxide (DMSO) 20 min before training. Then, the animals were placed in the white compartment, the central door was opened and the time spent for crossing between compartments was recorded. After the fish crossed the line between compartments a 45 g weight was dropped. This procedure was done five times in a row. Immediately after the fifth trial, the fish were injected intraperitoneally (i.p.) with either saline or CPA (0.4, 1.0, 4.0, 8.0 or 16 mg/kg). On the next day (test) the time to cross was recorded again. On the training trials, the animals treated with DMSO or haloperidol presented a significant increase in the latencies indicating learning (Friedman P = 0.0062 and 0.0001). The latencies in the test day showed that groups pre-treated with haloperidol and treated with CPA presented a dose-dependent increase in latencies, and those treated with the 16 mg/kg CPA group showed a significant increase (ANOVA two-way followed by Student-Newman-Keuls (SNK) P < 0.01). Thus, it can be suggested that the facilitatory action occurs due to an additive interaction between both systems, in a dose-dependent way.