Biomedical subjects

S Morato

Publications and source records attributed to S Morato.

15 recordsLinked to original sources

PubMed2004

Effect of the blockade of mu1-opioid and 5HT2A-serotonergic/alpha1-noradrenergic receptors on sweet-substance-induced analgesia.

RATIONALE: Sweet-substance-induced analgesia has been widely studied, and the investigation of the neurotransmitters involved in this antinociceptive process is an important way for understanding the involvement of the neural system controlling this kind of antinociception. OBJECTIVE: The aim of this study was to investigate the involvement of opioid and monoaminergic systems in sweet-substance-induced analgesia. METHODS: The present work was carried out in an animal model with the aim of investigating whether acute (24 h) or chronic (14 days) intake of a sweet substance, such as sucrose (250 g/l), is followed by antinociception. Tail withdrawal latencies in the tail-flick test were measured before and immediately after this treatment. Immediately after the recording of baseline values, independent groups of rats were submitted to sucrose or tap-water intake and, after chronic treatment, they were pretreated with intraperitoneal administration of (1) naltrexone at 0.5, 1, 2 or 3 mg/kg; (2) naloxonazine at 5, 10, 20 or 30 mg/kg; (3) methysergide at 0.5, 1, 2 or 3 mg/kg; (4) ketanserin at 0.5, 1, 2 or 3 mg/kg; or (5) physiological saline. RESULTS: Naltrexone and methysergide at two major doses decreased sweet-substance-induced analgesia after chronic intake of a sweet substance. These effects were corroborated by peripheral administration of naloxonazine and ketanserin. CONCLUSIONS: These data give further evidence for: (a) the involvement of endogenous opioids and a mu1-opioid receptor in the sweet-substance-induced antinociception; (b) the involvement of monoamines and 5HT2A serotonergic/alpha1-noradrenergic receptors in the central regulation of the sweet-substance-produced analgesia.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2003

Effects of septal cholinergic lesion on rat exploratory behavior in an open-field.

The medial septum participates in the modulation of exploratory behavior triggered by novelty. Also, selective lesions of the cholinergic component of the septohippocampal system alter the habituation of rats to an elevated plus-maze without modifying anxiety indices. We investigated the effects of the intraseptal injection of the cholinergic immunotoxin 192 IgG-saporin (SAP) on the behavior of rats in an open-field. Thirty-nine male Wistar rats (weight: 194-230 g) were divided into three groups, non-injected controls and rats injected with either saline (0.5 microl) or SAP (237.5 ng/0.5 microl). Twelve days after surgery, the animals were placed in a square open-field (120 cm) and allowed to freely explore for 5 min. After the test, the rats were killed by decapitation and the septum, hippocampus and frontal cortex were removed and assayed for acetylcholinesterase activity. SAP increased acetylcholinesterase activity in the septum, hippocampus and frontal cortex and decreased the total distance run (9.15 +/- 1.51 m) in comparison to controls (13.49 +/- 0.91 m). The time spent in the center and at the periphery was not altered by SAP but the distance run was reduced during the first and second minutes (2.43 +/- 0.36 and 1.75 +/- 0.34 m) compared to controls (4.18 +/- 0.26 and 3.14 +/- 0.25 m). SAP-treated rats showed decreased but persistent exploration throughout the session. These results suggest that septohippocampal cholinergic mechanisms contribute to at least two critical processes, one related to the motivation to explore new environments and the other to the acquisition and storage of spatial information (i.e., spatial memory).

Acetylcholinesterase↗

PubMed2003

Profile of wild Neotropical spiny rats (Trinomys, Echimyidae) in two behavioral tests.

The performance of three closely related species of spiny rats was compared in the elevated plus-maze and in the open-field tests. Laboratory rats were also evaluated. It was hypothesized that such tests should reveal differences in anxiety and exploratory profile among the wild species, which differ with respect to habitat, type of social organization and locomotion pattern. No consistent differences were found among the spiny rats, as assessed by conventional parameters, while such differences were detected between the domesticated lines. The social spiny rats (Trinomys yonenagae), which live in dunes, differed from the solitary sylvan species (T. iheringi and T. albispinus) in only one index of anxiety (open arms end-exploring). Nevertheless, thigmotaxis in novel environments exists in these spiny rats just as it does in the laboratory rats. During the tests, the sylvan species relied on erratic movements and T. iheringi was the most active species, whereas T. yonenagae employed vigilance and direct escape locomotion. This latter feature may be due to challenges imposed by open environments. Defecation score was reduced for all wild rats: it may represent a predation avoidance response. Concerning ethological measures, T. iheringi presented the highest scores of grooming, in both test situations, and T. albispinus the highest scores of rearing in the open-field. The great within-species variability found in the spiny rats may have concealed anxiety differences among them, despite the ability of both tests to reveal plesiomorphic behavioral characteristics, such as thigmotaxis. Our results also support the use of ethological approach in these tests.

Animals↗

PubMed2001

Vibrissal sense is not the main sensory modality in rat exploratory behavior in the elevated plus-maze.

Four groups of male Wistar rats were submitted to acute bilateral removal of mystacial vibrissae at different lengths from the follicle. Each group was divided into two subgroups, tested under high (150 Lux) and low environmental illumination (2 Lux). All the subjects were allowed to freely explore an elevated plus-maze for 5 min. Results indicated that rats tested under low illumination tended to explore the open arms more frequently and longer then rats tested under high illumination. When tested under low illumination, rats in the group that suffered whole vibrissa removal stayed longer in the open arms than those in the other groups but did not differ in the number of entries. The average increase in the length of open arm entries, rather than a decrease in aversion to the open arms, may be due to the need of more time to obtain information about the environment since there is no light and the vibrissae were removed. This effect was not seen with rats tested under high illumination, possibly because vision could be used to obtain relevant information.

Animals↗

PubMed2001

Facilitatory effect of substance P on learning and memory in the inhibitory avoidance test for goldfish.

The aim of this study was to investigate if substance P (SP) can improve learning and memory processes in goldfish, using an inhibitory avoidance test. A two-compartment aquarium with a central sliding door was used. The animals were placed in the white compartment, and after 20 s the door was opened. As they entered the dark compartment, a weight was dropped in front of them. This procedure was repeated three times. After training, the animals were injected intraperitoneally with SP or vehicle. Twenty-four hours after training, the animals were tested and their latency was recorded. The group injected with SP showed an increase in the latency on the test day as compared with the vehicle group. These results suggest SP can facilitate memory in goldfish in an inhibitory avoidance test.

Animals↗

PubMed2000

Dissociation of memory and anxiety in a repeated elevated plus maze paradigm: forebrain cholinergic mechanisms.

The effect of intraseptal injection of the cholinergic immunotoxin 192-IgG-saporin on behavior in the elevated plus maze was investigated. A 5-min test-retest paradigm, with minute-by-minute analysis of the first session, was used to evaluate both anxiety and memory in this task. Biochemical analyses revealed a decrease in acetylcholinesterase (AChE) activity in the hippocampus (HPC), septum, and frontal cortex of animals injected with IgG-192 saporin (237.5 ng) when compared with controls. No statistical differences were found between groups in terms of behaviors associated with locomotor activity, conventional measures of anxiety, or ethological behaviors during either session 1 or 2. During test session 2 the controls exhibited decreased exploratory activity and increased indices of anxiety. In contrast, the saporin-treated rats did not exhibit these experience-dependent behavioral changes from session 1 to 2. The minute-by-minute analysis showed a significant decrease in exploratory as well in anxiety associated behaviors during the first session for the control group, but not for the saporin-treated group. These results suggest that the cholinergic innervation of the HPC, the frontal cortex, or both forebrain structures, modulate the initiation of exploratory activity which, results in the acquisition and retention of spatial information, but does not affect the expression of anxiety in the elevated plus-maze.

Acetylcholinesterase↗

PubMed2000

Anxiety-like behavior in rats: a computational model.

This work describes a neural network model of the rat exploratory behavior in the elevated plus-maze, a test used to study anxiety. It involves three parameters: drive to explore; drive to avoid aversive stimuli; and spontaneous locomotor activity. Each network unit corresponds to a specific location in the maze and the connections, only between closest neighbors, represent the possible adjacent places to which a virtual rat can navigate. Competitive learning is used to generate a sequence of network states that correspond to the virtual rat successive locations in the maze. To evaluate the generality of the model it was also tested for two modifications of the elevated plus-maze: one with totally closed arms and the other with totally open arms. The results are compared with data obtained with rats. The simulations are consistent with experimental evidence and may provide an efficient way of describing the anxiety-like rat behavior in the elevated plus-maze. This could be useful for researching the emotional parameters involved in this anxiety animal model.

Animals↗

PubMed1999

A comparative study of the effects of morphine in the dorsal periaqueductal gray and nucleus accumbens of rats submitted to the elevated plus-maze test.

We studied the effects of morphine injected either systemically or into the dorsal periaqueductal gray (DPAG) or nucleus accumbens (NA) using conventional and ethological analyses of behavior of rats submitted to the elevated plus-maze test with transparent walls. Intraperitoneal morphine (0.1 mg/kg and 0.3 mg/kg) increased both standard and ethological measures, expressing general exploratory activity such as total arm entries, end-exploration, scanning, head-dipping, and rearing. Morphine 10 (7.6 microg/microl) and 30 nmol (23 microg/microl) injected into nucleus accumbens produced similar effects, which were blocked by i.p. naltrexone (2.0 mg/kg), an opioid antagonist with good affinity for mu-opioid receptors. Morphine injected into the DPAG produced either antiaversive (10 nmol) or aversive effects (30 nmol), which respectively reduced and increased entries and time spent in the open arms and behaviors associated with risk assessment (peeping out, stretched attend postures, and flat back approach). The proaversive effects were inhibited by i.p. norbinaltorphimine (2.0 mg/kg), a selective inhibitor for kappa-opioid receptors. These findings support the contention that at least some of the motivational effects of morphine may be due to activation of opioid mechanisms in nucleus accumbens, and DPAG has neural substrates for antiaversive and aversive effects of morphine. Moreover, on the basis of previous and present data obtained in this laboratory, it is suggested that stimulation of mu-opioid receptors inhibits and stimulation of kappa-receptors activates the neural substrate of aversion in the DPAG. On the other hand, the increase in exploratory behavior due to interaction of morphine with mu-opioid receptors in the nucleus accumbens may be due to the stimulation of the interface between neural substrates of motivation and motor output in this structure.

Analgesics, Opioid↗

PubMed1999

Ethopharmacological analysis of 5-HT ligands on the rat elevated plus-maze.

The present study investigated the behavioral effects of five 5-HT agonists and antagonists in the rat elevated-plus-maze using conventional and ethologically derived measures. An anxiolytic effect of the 5-HT1A agonist ipsapirone (0.25, 0.75, and 2.25 mg/kg) was detected by risk-assessment and scanning but not by percentage of open-arm entries and time spent on open arms. Anxiogenic effects of the 5-HT2C agonist TFMPP (0.1, 0.2, and 0.4 mg/kg) and 5-HT2A antagonist SR 46349B (1, 3, and 10 mg/kg) were detected by percentage of open-arm entries, time spent on open arms, scanning, end exploring, but not by risk assessment. Finally, the effects of the 5-HT3 antagonist BRL 46470 A (0.001, 0.01, and 0.1 mg/kg) and 5-HT(2A/C) antagonist RP 62203 (0.25, 1, and 4 mg/kg) were scarce in both conventional and ethologically derived measures. These results are indicative that ethological measures may sometimes be more sensitive than the standard ones, and should be used together with them when assessing serotonergic or any other novel drugs in the elevated plus-maze.

Animals↗

PubMed1997

Sucrose ingestion causes opioid analgesia.

The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l) for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean +/- SEM, N = 12) for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 +/- 0.04, 0.10 +/- 0.05, 0.15 +/- 0.08 and 0.49 +/- 0.07, respectively. One-way ANOVA indicated a significant difference (F(3, 47) = 9.521, P < 0.001) and the Tukey multiple comparison test (P < 0.05) showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7) receiving sucrose exhibited an analgesia index of 0.20 +/- 0.10 while rats receiving only sucrose (N = 7) had an index of 0.68 +/- 0.11 (t = 0.254, 10 degrees of freedom, P < 0.03). This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

Analgesia↗

PubMed1997

Paradoxical increase of exploratory behavior in the elevated plus-maze by rats exposed to two kinds of aversive stimuli.

Albino rats were submitted to a 24-h period of social isolation (individual housing) combined with 0, 1, 2 or 3 twenty-four-hour periods of exposure to different vivaria (novelty) and tested in the elevated plus-maze. Results, reported as mean +/- SEM for N = 12, show that the time (in seconds) spent in the open arms by rats exposed to novelty for 0, 1, 2 and 3 days was 28.3 +/- 4.4, 31.6 +/- 3.2, 29.1 +/- 3.5 and 25.0 +/- 3.3, respectively, when grouped in the same vivarium; 29.6 +/- 2.7, 7.6 +/- 2.1, 9.6 +/- 4.4 and 28.5 +/- 3.7 when grouped in different vivaria; 2.9 +/- 1.1, 1.8 +/- 1.0, 2.7 +/- 1.1 and 0 +/- 0 when isolated in the same vivarium, and 2.6 +/- 1.1, 31.5 +/- 8.2, 24.8 +/- 4.2 and 0 +/- 0 when isolated in different vivaria. The number of entries into the open and closed arms followed a similar trend. This indicates that, separately, both exposure to novelty and isolation are aversive manipulations. Paradoxically, when novelty was combined with a concomitant 24-h period of social isolation prior to testing, the decrease in exploratory behavior caused by either of the two aversive manipulations alone was reverted. These results are indicative that less intense anxiety triggers mechanisms mediating less energetic behavior such as freezing, while higher levels trigger mechanisms mediating more vigorous action, such as flight/fight behavior, since the combination of two aversive situations resulted in more exploratory behavior than with either alone. They are also suggestive of habituation to the effects of novelty, since exposure to it for 3 days produced exploratory behavior similar to that of controls.

Animals↗

PubMed1995

Feeding patterns of rats when food-access cost is alternately low and high.

Rats living in a laboratory foraging paradigm began each meal by bar pressing to procure access to food and then could eat any amount. In different conditions the procurement price changed from low (10 bar presses) to high (200 or 400 bar presses) every ten days, five days, or one day, or on schedules of one-day-low/two-days-high, or one-day-low/four-days-high. In a final condition, the price alternated at every meal. Meals were less frequent and larger on high-price days. In the ten- and five-day alternations, the rats adjusted meal frequency on the first day of a price, but changed meal size gradually over the first few days; by the fifth day, daily intake was not different on low- and high-price days. In the one-day alternations, the rats ate less food, and in some cases did not eat at all, on high-price days, and lost weight. Intake was greater than normal, and body weight recovered, on low-price days. This pattern saved foraging cost at the expense of greater-than-normal daily fluctuations in food intake and body weight. When two or four days of high price alternated with one day of low price, the rats did eat on the first day of high price, suggesting they may integrate costs over a time window greater than 24 h.

Animals↗

PubMed1993

Role of resocialization and of 5-HT1A receptor activation on the anxiogenic effects induced by isolation in the elevated plus-maze test.

Rats were isolated for periods varying from 1 h to 2 weeks and the exploratory activity of these animals on the elevated plus-maze was studied. Rats isolated from periods of 2 h on displayed a significant reduction in the number of entries and time spent in the open arms of the plus-maze compared to socially housed controls. This effect was not correlated with the decrease in the total number of entries also produced by isolation. Acute treatment with midazolam or resocialization for a 24-h period clearly reversed these responses produced by prior 2-h isolation in the elevated plus-maze. It is suggested that exposure to a 2-h isolation period could be a useful nonpharmacological means of generating anxiety in laboratory rodents. Chronic treatment, but not acute treatment, with gepirone, a 5-HT1A agonist, inhibited the anxiogenic effects caused by a 2-week period of isolation. The reduction in aversiveness promoted by resocialization may be due to a recovery in the 5-HT activity depressed by isolation in a much faster way than observed with chronic gepirone administration.

Animals↗

PubMed1992

Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze.

Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors. As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.

Analysis of Variance↗

PubMed1989

Effects of floor surface and environmental illumination on exploratory activity in the elevated plus-maze.

We determined the effects of floor surface (wire mesh, WM+, or smooth wood, WM-) and environmental light intensity (20 or 1200 lux) on the exploratory activity of rats in an elevated plus-maze using 15 rats in each group. Rats tested on the wire-mesh floor under low environmental light intensity presented a two-fold increase in the total number of arm entries compared to WM+/high light, WM-/high light or WM-/low light. The relative frequency of open arm entries was greater under WM+/low light (38 +/- 3% vs 20 +/- 5%, 19 +/- 3% and 13 +/- 3% for WM-/low light, WM+/high light and WM-/high light, respectively), as was the percent of time spent in the open arms (27 +/- 4% vs 9 +/- 3%, 8 +/- 2% and 5 +/- 1% for WM-/low light, WM+/high light and WM-/high light, respectively). These behaviors are associated with "aversiveness" as measured with this test. The present results demonstrate that baseline values for drug studies may be decreased or increased by selecting the appropriate type of floor surface and intensity of environmental illumination, thereby permitting more sensitivity, and thus selectivity, for measuring anxiolytic or anxiogenic drug effects, respectively.

Animals↗