Number Of Fecal Boli Research Articles

Effects of paradoxical sleep deprivation on oxidative parameters in the serum and brain of mice submitted to the animal model of hyperglycemia

The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36 h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.

Acute Intermittent Hypoxia Therapy alters Cognitive Behavioral Parameters in Wistar Albino Rats

Cognitive disorders, including dementia and Alzheimer’s disease, pose substantial global health challenges, demanding effective prevention and treatment strategies. Intermittent hypoxia therapy (IHT), involving brief exposures to reduced oxygen levels, is a novel approach with potential cognitive benefits. This study investigates the effects of IHT on cognitive behavior in wistar albino rats through comprehensive behavioral experiments, including the open field test (OFT) and Morris water maze (MWM). The results reveal that IHT promotes locomotor activity, reduces anxiety-related behaviors, and positively impacts cognitive flexibility. In the OFT, the IH group exhibited increased grid crossings and distance traveled, indicating heightened locomotion, which may be associated with cognitive improvement. Furthermore, IH significantly reduced thigmotaxis behavior and the number of fecal boli, indicating reduced anxiety levels compared to the control group. While IHT did not significantly enhance spatial memory acquisition in the MWM, it improved platform recognition during the probe test. The IH group spent more time in the target quadrant, suggesting enhanced memory retrieval and recognition. Additionally, in the reverse MWM, IH demonstrated moderate improvements in cognitive flexibility, with faster latency on trial 1. These findings suggest that IHT holds promise as a non-invasive intervention for cognitive enhancement, particularly in terms of locomotor activity, anxiety reduction, and certain aspects of memory and cognitive flexibility. Further research is warranted to elucidate the underlying mechanisms and explore the potential therapeutic applications of IHT in cognitive disorders. In summary, this study highlights the cognitive benefits of IHT in rats, paving the way for future investigations and potential clinical applications in the realm of cognitive disorders.

Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde

BackgroundSleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. MethodsSleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD−FT+). The second group received SD without FT(SD+FT−). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. ResultsSD did not lead to any significant difference in nociceptive behaviors in FT between groups SD−FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SD+FT+. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05). ConclusionSD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Genome-wide association study in a rat model of temperament identifies multiple loci for exploratory locomotion and anxiety-like traits.

Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability to these disorders. To model these heritable tendencies, we selectively bred rats for high and low exploration in a novel environment [bred High Responders (bHR) vs. Low Responders (bLR)]. To identify genes underlying the response to selection, we phenotyped and genotyped 538 rats from an F2 cross between bHR and bLR. Several behavioral traits show high heritability, including the selection trait: exploratory locomotion (EL) in a novel environment. There were significant phenotypic and genetic correlations between tests that capture facets of EL and anxiety. There were also correlations with Pavlovian conditioned approach (PavCA) behavior despite the lower heritability of that trait. Ten significant and conditionally independent loci for six behavioral traits were identified. Five of the six traits reflect different facets of EL that were captured by three behavioral tests. Distance traveled measures from the open field and the elevated plus maze map onto different loci, thus may represent different aspects of novelty-induced locomotor activity. The sixth behavioral trait, number of fecal boli, is the only anxiety-related trait mapping to a significant locus on chromosome 18 within which the Pik3c3 gene is located. There were no significant loci for PavCA. We identified a missense variant in the Plekhf1 gene on the chromosome 1:95Mb QTL and Fancf and Gas2 as potential candidate genes that may drive the chromosome 1:107Mb QTL for EL traits. The identification of a locomotor activity-related QTL on chromosome 7 encompassing the Pkhd1l1 and Trhr genes is consistent with our previous finding of these genes being differentially expressed in the hippocampus of bHR vs. bLR rats. The strong heritability coupled with identification of several loci associated with exploratory locomotion and emotionality provide compelling support for this selectively bred rat model in discovering relatively large effect causal variants tied to elements of internalizing and externalizing behaviors inherent to psychiatric and substance use disorders.

Флавоноид кверцетин уменьшает двигательную активность и повышает эмоциональную реактивность у крыс

This work is aimed at the investigation of the effects of polyphenolic flavonoid quercetin, possessing a wide range of pharmacological properties, on locomotor, emotional and anxiety-like behavior in rats under normal conditions. Intraperitoneal administration of quercetin at a dose of 5 mg/kg was found to induce several types of anxiety-like behavior in the open field (OF) test 2 hours after the injection. It was characterized by reduced time spent in the central zone of the arena, and increased — in the peripheral zone. Such effects were absent in the elevated plus maze (EPM) test. Additionally, quercetin induced an enhanced emotional reactivity in the OF test that manifested in a prolonged freezing duration and the increased number of fecal boli. A considerable decrease in the level of horizontal activity was detected in this test: the number of squares crossed in the peripheral and the central zones was decreased. Moreover, the number of supported rearings was decreased in both tests, which reflects an attenuation of the exploratory behavior. These findings indicate the anxiogenic action of quercetin. Elicited behavioral changes induced by quercetin were not linked to changes in the stress-induced protein Hsp70 content in the brain structures implicated in locomotion and emotion regulation. We propose that the decreased locomotor activity and increased emotional reactivity following quercetin administration in rats are associated with its modulatory effects on the intracellular kinase signaling pathways that play an important role in the neurobiological processes.

Acute treatment with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one produces behavioral changes and inhibition of creatine kinase activity in the brain of rats

Organotellurium compounds have been synthesized since 1840, but their pharmacological and toxicological properties are still incipient. Therefore, the objective of this study was to verify the effect of acute administration with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on the activity of brain creatine kinase (CK), a key enzyme in energy metabolism, and on behaviors in the open field test of 30-day-old rats. Animals were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and after 55 min of the drug administration the open field test was carried out. Behavior analyses were performed during 5 min and the number of the squares crossed, number of rearing, number of groomings and number of fecal boli were recorded by an observer. Then, the animals were sacrificed and the cerebral cortex, the hippocampus, and the cerebellum were dissected, and CK activity and sulfhydryl content were measured in the brain. The organotellurium increased the ambulation and rearing behaviors in the open field test at doses of 250 and 500 μg/kg. Moreover, the compound inhibited CK activity and provoked a reduced of thiol content measured by the sulfhydryl assay in all the tissues studied. Therefore, changes in energy homeostasis and motor behavior in rats treated with this organotellurium support the hypotheses that the brain is a potential target to pharmacological and toxicological effects of this compound.

Light-dark box as a model of state anxiety in Kunming mice: test-retest reliability and correlations between parameters

Objective To explore the test-retest reliability and correlations of the light-dark box (LDB).Methods The behavior of mice in LDB was recorded twice, for five minutes,with a one-week inter-trial interval.Following parameters were evaluated:latency time for the first entry into the dark area (Latence); percentage of time exploring in the light area ( Ltime％ ); percentage of squares crossing in the light area ( Lcross％ ); total number of squares crossing ( Cross ); percentage of rears in the light area ( Lrear％ ); total number of rears (Rear); total score (Total); transitions between two areas (Transition); and number of fecal boli (Fbi). Subsequently,the intraclass correlation coefficient (ICC), the Kappa agreement coefficient (Kappa) and the Pearson correlation coefficient (Pearson) were calculated for these parameters. Results ①ICC for Lrear％ ( ICC =0.5207, P＜0.01 ) showed a fair reliability. ②Kappa for all parameters indicated a poor reliability. ③Pearson displayed weak negative correlations between Transition and Ltime％ ( Pearson = - 0.4030, P ＜ 0.05; Pearson =- 0. 1490, P＞ 0. 05 ), Lcross％ ( Pearson = - 0. 4331, P ＞ 0. 05; Pearson = - 0.1893, P ＞ 0.05 ), Lrear％ ( Pearson = - 0. 4485, P ＜ 0. 05; Pearson = 0. 02845, P ＞ 0. 05 ), however, fair positive correlations between Transition and Cross (Pearson =0. 8603, P＜0.01; Pearson =0.6341, P＜0. 01 ) ,Rear(Pearson =0.4271, P＞0. 05;Pearson = 0. 7245, P ＜ 0. 001 ). Conclusion Rear is found to be stable over time, and indicated a fair reliability.There is a weak negative correlation between Transition and Ltime％, Lcross％, Lrear％, but fair positive correlations between Transition and Cross, Rear. Key words: Light-dark box; Kunming mice; State anxiety; Animal model; Test-retest reliability; Correlation

The open field test as a method for ethology in Kunming mice: test-retest reliability

Objective To explore the test-retest reliability of the open field test,as a method for ethology in Kunming mice. Methods The behavior of adult male Kunming mice in the open field test was recorded twice,once for five minutes, with a one-week inter-trial interval. The following parameters were evaluated:number of central squares; number of peripheral squares; percent of central squares; number of horizontal squares; number of rearings; total score; and number of fecal boli. Subsequently,the intraclass correlation coefficient (ICC) and the agreement index (Kappa) were calculated for each of these parameters. Results Both ICC and Kappa for total score( ICC =0.902, P＜0.01; Kappa =0.680, P＜0.01; r=0.815, P＜0.01 ) showed a good reliability and correlation between the test trials. Only ICC for number of central squares ( ICC = 0. 578, P ＜ 0.01 ), number of peripheral squares( ICC =0.615, P＜0.01 ) ,percent of central squares(ICC=0.523, P＜0.01) ,number of horizontal squares( ICC = 0. 607, P ＜ 0.01 ) and number of rearings ( ICC = 0. 606, P ＜ 0.01 ) indicated a fair reliability between the test trials. Neither ICC nor Kappa for number of fecal boli displayed a significant reliability between the test trials. The difference of these parameters between test and retest, such as number of peripheral squares( t =3.01, P＜0.01 ),number of horizontal squares( t = 3.34, P ＜ 0.01 ) and total score( t = 7.86, P ＜ 0.01 ) were significant. Conclusion The parameter,total score for Kunming mice in the open field test,is found to be stable over time, and indicates a good reliability with a one-week inter-trial interval. Key words: Open field test; State anxiety; Ethology; Test-retest reliability; Kunming Mice

Genetic correlates of morphine withdrawal in 14 inbred mouse strains

Male mice from 14 standard inbred strains were exposed to morphine in a sustained released preparation injected subcutaneously. Five hours later withdrawal was precipitated by intraperitoneal injection of naloxone. Mice were tested from 0 to 15min after naloxone for withdrawal jumping behavior, and then from minute 15–16 for other signs, including boli count, presence of soft stool, lacrimation, “wet dog” shakes, and air chewing. They were also assessed for change in body temperature 17min after naloxone. Strains differed markedly in the severity of withdrawal for jumping, change in body temperature, and number of fecal boli. Strains also differed in percentage of animals displaying soft stool and air chewing behavior. The other two signs were seen at too low frequency for analysis. Correlations of strain mean withdrawal severity with other responses to morphine and other abused drugs showed that high morphine withdrawal jumping and low change in body temperature were both genetically related to high morphine consumption, but not generally to other measures of morphine withdrawal or morphine sensitivity.

Morphine induced tolerance to mouse intestinal but not colonic transit and constipation

The objectives of the present studies were to compare the development of tolerance to antinociception, constipation, intestinal and colonic transit in the mouse. Eight‐ (morphine pellet) and 45‐ (morphine pellet plus supplemental injections) fold antinociceptive tolerance to morphine were developed by standard techniques. Defecation was measured daily as the number of fecal boli and weight of feces. In both tolerant groups defecation was significantly reduced at 24h, 48h and 72h, compared to placebo‐pelleted mice, indicating that tolerance did not develop to morphine‐induced constipation. The effects of a 10 mg/kg dose of morphine on antinociception, intestinal and colonic transit were determined 72h following pellet‐implantation. Acute morphine reduced intestinal transit of a charcoal meal administered orally by 50% in placebo‐pelleted mice but did not produce a similar reduction in animals chronically exposed to morphine indicating the development of tolerance. The time for the expulsion of a glass bead inserted 3 cm proximal to the anus was used to measure colonic transit. Acute morphine significantly reduced the bead expulsion time in both placebo‐ and morphine‐pelleted mice indicating no tolerance. These findings confirm that chronic morphine produces tolerance to antinociception and intestinal transit but not to colonic transit or defecation. Supported by DK46367, DA01647, DA020836

5-hydroxytryptamine release in the anterior hypothalamic and the hippocampal areas of cholestatic rats

Cholestasis contributes to the genesis of fatigue through several mechanisms. Among these mechanisms, affected serotonergic neurotransmission is important in the pathogenesis of central fatigue. Previously, elevated levels of 5-hydroxyindole acetic acid (5-HIAA), the metabolite of 5-hydroxytryptamine (5-HT) and increased 5-HT 2 receptor density were demonstrated in the anterior hypothalamus and in the hippocampus of bile duct resected rats (BDR), respectively. The aim of this paper is to demonstrate evoked 5-HT release in selected brain regions like anterior hypothalamus and hippocampal CA1 regions of cholestatic rats using BDR rats as an experimental model for cholestasis. In this study, we analyzed the K + evoked 5-HT and its metabolite 5-HIAA levels by using HPLC with electrochemical detection in the microdialysis samples collected from anterior hypothalamic and hippocampal CA1 regions of sham-operated and BDR rats ( n = 6). The ratios of [5-HIAA] to [5-HT] following perfusion with 100 mM K + artificial cerebrospinal fluid was used for the comparison of the evoked release of 5-HT. Locomotor activity was used to assess the signs of cholestasis associated fatigue in the BDR rats. The vertical and horizontal activity counts within 15 min were found to be decreased in the BDR rats compared to sham-operated rats ( p < 0.05). Besides, the number of fecal boli (an index of emotionality) was also significantly fewer in the cholestatic rats ( p < 0.05). No significant difference between the sham-operated and the BDR rats was detected in the basal 5-HT and 5-HIAA levels of anterior hypothalamus. K + stimulation yielded a more profound increase in the [5-HIAA] / [5-HT] in the BDR rats ( p < 0.05). The basal levels of 5-HT in CA1 region of the BDR rats was found to be lower than that of sham-operated group ( p < 0.05), but no significant difference was observed in terms of evoked 5-HT release in both sham-operated and BDR rats. These findings imply the presence of affected serotonergic system in cholestasis.

Novel Actions of Estrogen Receptor-β on Anxiety-Related Behaviors

Estrogens are reported to have both anxiogenic and anxiolytic properties. This dichotomous neurobiological response to estrogens may be mediated by the existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. In brain, ERalpha plays a critical role in regulating reproductive neuroendocrine function, whereas ERbeta may be more important in regulating nonreproductive functions. To determine whether estrogen's anxiolytic actions could be mediated by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists. Ovariectomized female rats, divided into four treatment groups, were injected with the selective ERbeta agonist diarylpropionitrile (DPN), the ERalpha-selective agonist propyl-pyrazole-triol (PPT), 17beta-estradiol, or vehicle daily for 4d. After injections, behavior was monitored in the elevated plus maze or open field. Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the elevated plus maze, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the open field, DPN-treated females made more rears, interacted more with a novel object, and spent more time in the middle of the open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions are ER mediated, the nonselective ER antagonist tamoxifen was administered alone or in combination with DPN. Tamoxifen blocked the previously identified anxiolytic actions of DPN. Taken together, these findings suggest that the anxiolytic properties of estrogens are ERbeta mediated.

Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test

Effect of blocking N-methyl- d-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 μl injections of saline, (±)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 μg) or 2,3 dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-( f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5, or 1 μg) 15 min before testing. Time spent in open arm, time per entry, end arrivals, open, closed, and total arm entries, relationship between open-, closed-, and total arm entries, rearing, face-, head-, and body grooming, and number of fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5 and 1 μg; P<.01) and NBQX (1 μg; P<.05) treatment, whereas time per entry was increased only with AP-7 (1 μg; P<.05). Open arm entries were increased by the intermediate doses of AP-7 (0.5 μg; P<.01) and NBQX (0.5 μg; P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5 μg/1 μl, P<.05). The frequency of rearing, grooming, and closed arm entries was not affected by the treatment. We conclude that NMDA and non-NMDA-glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical influences with the median doses, but that at higher doses the blockers have an anxiolytic-like effect.

Activation of somatodendritic 5-HT 1A autoreceptors in the median raphe nucleus disrupts the contextual conditioning in rats

We have shown that the median raphe nucleus (MRN) is involved in the control of contextual fear conditioning. Also, electrolytic lesion in the MRN causes signs of behavioral disinhibition, with an increase in locomotor activity measured in an open field. In this work, we have extended this study by analyzing the behavioral and autonomic responses in a contextual conditioning paradigm in rats with either neurochemical lesions from N-methyl- d-aspartate (NMDA), or microinjected with 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT) in the MRN. The animals received NMDA, 8-OH-DPAT or saline microinjections into the MRN before the conditioning experiments, during which they were subjected to ten conditioning trials in an experimental chamber (same context) where they received foot-shocks (0.7 mA, 1 s with 20 s intervals). The next day, the animals were tested again either in the same or in a different experimental chamber, where the duration of freezing, number of rearings, bouts of micturition and number of fecal boli were recorded. Control rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly inhibited in rats with NMDA lesions or with 8-OH-DPAT microinjections into the MRN. These MRN manipulations also produced a reduction in micturition. Such effects were context-specific since 8-OH-DPAT in MRN did not affect fear conditioned responses to tone previously associated with foot-shocks. In the open-field test, rats with neurotoxic lesions or with 8-OH-DPAT microinjections into the MRN had higher horizontal locomotor activity than control rats, without the number of rearings changing. As rats injected with 8-OH-DPAT into the MRN may freeze to a tone in a conditioned test paradigm and also show increased activity in an open field test the functional role of MRN on locomotor activity and contextual fear conditioning are clearly dissociated. Altogether, these results clearly show that such 5-HT mechanisms of the MRN serve as a neural substrate for the storage process of the context fear.

Effects of acute topiramate dosing on open field behavior in mice

Although topiramate (TPM) has been used to treat human disease, there are few studies of its effects on the behavior of animal models. Objective. This study aimed to assess the effect of acute TPM administration on the behavior of mice undergoing the open-field test. Method. The animals were divided in two groups: the treatment group (n = 10), which received 10 mg/kg TPM intraperitoneally, and the control group (n = 10), which received saline. 30 minutes after drug administration, the animals were assessed for 5 minutes in the open-field. The following parameters were analyzed: number of squares explored, immobility time, central area permanence time, peripheral apparatus permanence time, rearing frequency and time, grooming frequency and time, rearing frequency during the last minute, number of fecal boli, and estimated speed. Results. The treatment group had a higher number of squares explored (p = 0.02) and greater estimated speed (p = 0.01). Conclusion. The results suggest that acute TPM administration increases the locomotor activity of mice without interfering with learning, anxiety, stress, and exploratory behavior.

Prolactin levels in juvenile and adult rats following acute restraint and the open field

Acute restraint and exposure to a novel environment alter behavior and increase prolactin levels in rats quickly and reliably. However, little research is available that examines behavior and levels of prolactin as a result of acute exposure to one stressor immediately followed by a second stressor. Similarly, a relationship between prolactin and behavior has not been established. In the present study, juvenile (35-day-old) and adult (5-month-old) rats were either placed in a novel open field for 10 min or restrained for 10 min prior to exposure to the open field. Restrained juveniles groomed more than control juveniles and restrained adults. Conversely, restraint + open field reduced ambulation and rearing among juvenile males and females, and adult females ambulated less than control females and restrained males across both behaviors. In addition, results from the present study demonstrated the first reported relationship between prolactin and open-field behaviors. Prolactin was positively correlated with rearing and number of fecal boli, and levels were negatively correlated with freezing. Among adult females, prolactin levels were lower following restraint + open field than after exposure only to the open field. This may be explained by the psychological response to the open field when it directly followed the physical stressor of acute restraint.

Regulation of contextual conditioning by the median raphe nucleus

The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. Electrical stimulation of this mesencephalic area causes behavioral and autonomic manifestations characteristic of fear such as, freezing, defecation and micturition. In this study we extend these observations by analyzing the behavioral and autonomic responses of rats with lesions in the MRN submitted to a contextual conditioning paradigm. The animals underwent electrolytic or sham lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later they were tested in an experimental chamber where they received 10 foot-shocks (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals were tested again either in the same or in a different experimental chamber. During this, the duration of freezing, rearings, bouts of micturition and number of fecal boli were recorded. Sham-operated rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN lesions also reduced the bouts of micturition and number of fecal boli. These rats showed a reduced number of rearings than sham-lesioned rats. This effect is probably the result of the displacement effect provoked by freezing since no significant differences in the number of rearings could be observed between these animals and the NMR-lesioned rats tested in an open field. This lesion produced higher horizontal locomotor activity in this test than the controls (sham-lesioned rats). These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it. Behavioral inhibition is also under control of MRN but its neural substrate seems to be dissociated from that of contextual fear.

Pharmacodynamics and kinetics of loss of tolerance and physical dependence on morphine induced by pellet implantation in the rat.

The decay characteristics of tolerance and physical dependence on morphine induced by a pellet implantation procedure were determined in male Sprague-Dawley rats. Rats were implanted subcutaneously with 6 morphine pellets during a 7-day period. The pellets were removed, and at various times thereafter tolerance to the analgesic and hyperthermic effects of morphine was measured by determining the response in rats implanted with morphine and placebo pellets. Similarly, the physical dependence was assessed by monitoring withdrawal signs following an injection of naloxone. A high degree of tolerance developed to the analgesic and hyperthermic effects of morphine. Similarly, a high degree of physical dependence also developed as evidenced by a high incidence of jumping response, teeth chattering and production of fecal boli induced by injections of naloxone. In addition, loss of body weight and body temperature also occurred. The analgesic and hyperthermic response to morphine recovered very gradually. There was no significant difference in the analgesic and hyperthermic responses to morphine on day 4 after the pellet removal in rats implanted with morphine and placebo pellets. The decay of tolerance was linear with time for the analgesic effect (r = 0.98) and for the hyperthermic effect (r = 0.93). The change in symptoms of physical dependence on morphine with time depended on the specific symptom monitored. The average number of jumps and teeth chattering decreased with time in a linear fashion with r values of 0.98 and 0.99, respectively. However, the number of fecal boli and wet dog shakes increased linearly with time (r = 0.97). The recovery of loss of body weight was also linear with time. Thus, it is clear that fecal boli and wet dog shakes, which increase in number as the dependence decays, are signs of a low degree of dependence. The results suggest that different central or peripheral mechanisms may be operating in different withdrawal symptoms. These studies may prove to be useful when studying the mechanisms involved in the induction and reversibility of tolerance and dependence processes, and in long-term effects of opiates at a time when the tolerance and physical dependence is no longer evident.