Male CF-1 Mice Research Articles

Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism

Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation.

Non-invasive echocardiographic studies in mice: Influence of anesthetic regimen

Transgenic murine models of cardiovascular disease offer great potential insights regarding mechanisms of human disease, but efficient and reliable methods for phenotype evaluation are necessary. We employed non-invasive echocardiography to evaluate hemodynamic parameters in mice, and evaluated statistical reliability of these parameters with respect to anesthesia regimen. Male CF-1 mice received inhaled halothane (0.25–0.75% in 95% O 2) or ketamine/xylazine (80/10mg/kg i.p.) and 2-dimensional, M-mode, and Doppler ultrasound imaging were used to assess cardiac contractility and aortic flow velocities. Halothane was more convenient and reliable with respect to rate of induction, reversal, and control of anesthetic depth. At comparable levels of anesthesia, ketamine/xylazine produced significant reductions in heart rate (308 ± 14 vs. 501 ± 14 bpm, p<0.001), left ventricular fractional shortening (41.7 ± 1.3 vs. 49.3 ± 1.0 %, p<0.001), and cardiac output (7.6 ± 0.5 vs. 11.5 ± 0.6 ml/min, p<0.001) when compared to halothane inhalation. No change in stroke volume or peak aortic velocity was observed. Correlation analyses revealed highly significant positive relationships between heart rate and fractional shortening (r= 0.61, p<0.002) and cardiac output (r= 0.88, p<0.001) but no relation to stroke volume or aortic velocity. Variability of intra-animal and intra-group parameter estimation were frequently 2-fold larger for ketamine/xylazine anesthesia vs. halothane. Statistical power analysis showed the increased measurement error for ketamine/xylazine leads to much larger numbers of mice/group to achieve identical statistical sensitivity. These data further illustrate the feasibility of echocardiography for rapid, non-invasive cardiovascular assessment in mice. However, several obtainable parameters are highly sensitive to both heart rate and anesthetic used and the choice and control of anesthetic are critical for physiologically relevant performance parameters and maximal ability to detect statistical differences among groups. Thus, for these non-invasive studies, inhalation anesthesia with agents such as halothane is superior to anesthesia induced by ketamine/xylazine administration.

NMDA antagonists block expression of sensitization of amphetamine- and apomorphine-induced stereotypy

We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both single and multiple pretreatment paradigms. In the present study, we tested whether NMDA receptor antagonists and an inhibitor of nitric oxide synthesis inhibit expression of sensitization in either of these models. Male CF-1 mice were pretreated with a single dose or with three daily doses of amphetamine (14 mg/kg) or apomorphine (40 mg/kg). Two days following these pretreatments, mice were injected with ((±)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP, 20 mg/kg), dizocilpine maleate (MK-801, 0.1 mg/kg), 7-nitroindazole (25 mg/kg), or vehicle 30 min before receiving amphetamine (7 mg/kg) or apomorphine (3 mg/kg). The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine, indicating that sensitization had developed. CPP, MK-801, and 7-nitroindazole prevented the expression of the sensitized stereotyped response induced by either amphetamine or apomorphine in both paradigms. These drugs did not attenuate the stereotypy elicited by amphetamine and apomorphine in drug-naı̈ve mice. The effect of 7-nitroindazole was reversed by pretreatment with 500 mg/kg of l-arginine but not by d-arginine. These results suggest that glutamatergic transmission and subsequent NMDA receptor activation and the production of nitric oxide play a critical role in the expression of the sensitized stereotyped behavioral response elicited by amphetamine or apomorphine.

Isolation and Characterization of a Novel ConusPeptide with Apparent Antinociceptive Activity

Isolation and Characterization of a Novel ConusPeptide with Apparent Antinociceptive Activity

NMDA glutamate receptor role in the development of context-dependent and independent sensitization of the induction of stereotypy by amphetamine or apomorphine

We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both a context-dependent and a context-independent paradigm. In the present study, we tested whether N-methyl- d-aspartate (NMDA) receptor antagonists prevent development of sensitization in either of these models. Male CF-1 mice were pretreated with 20 mg/kg (+)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP), 0.1 mg/kg (+)5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohopten-5,10-imine maleate (MK-801, dizocilpine maleate), or 25 mg/kg 7-nitroindazole 30 min before a single dose (context-dependent paradigm) or each of three daily doses (context-independent paradigm) of 14 mg/kg amphetamine or 40 mg/kg apomorphine. Two days following this pretreatment, mice were injected with 7 mg/kg amphetamine or 3 mg/kg apomorphine. The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine alone, indicating that sensitization had developed. Both CPP and MK-801 prevented the development of sensitization in the context-dependent model but not in the context-independent paradigm. 7-Nitroindazole did not attenuate development of sensitization in either model. The results suggest that activation of glutamatergic receptors is important in some sensitization paradigms but not others, indicating that glutamate can be important but is not always required for the development of sensitization.

Importance of Environmental Context in the Development of Amphetamine- or Apomorphine-Induced Stereotyped Behavior After Single and Multiple Doses

The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or apomorphine differ in the context dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg, IP) or apomorphine (40 mg/kg, SC) only became sensitized to a lower test dose of amphetamine (7 mg/kg, IP) or apomorphine (3 mg/kg, SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with three high doses (24 h apart) of amphetamine (14 mg/kg, IP) or apomorphine (40 mg/kg, SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg, IP) or apomorphine (3 mg/kg, SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization of amphetamine- or apomorphine-induced stereotyped behavior.

Importance of Environmental Context in the Development of Amphetamine- or Apomorphine-Induced Stereotyped Behavior After Single and Multiple Doses

The present study was designed to determine whether single and repeated pretreatment regimens with amphetamine or apomorphine differ in the context-dependency of sensitization of stereotyped behavior. Male CF-1 mice that were pretreated with a single high dose of amphetamine (14 mg/kg intraperitoneally [IP]) or apomorphine (40 mg/kg subcutaneously [SC]) only became sensitized to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in an environment that was the same as the pretreatment environment. However, animals pretreated with 3 high doses (24-h apart) of amphetamine (14 mg/kg IP) or apomorphine (40 mg/kg SC) did demonstrate sensitization to a lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in an environment that was different from the pretreatment environment. Context-dependent sensitization, but not context-independent sensitization, was extinguished by pairing the test environment with saline injections instead of drug injections. In addition, it was determined that neither sensitization model could be related to pharmacokinetic factors. Therefore, the results indicate that repeated exposure to amphetamine or apomorphine overcomes the context-dependent component of sensitization of amphetamine- or apomorphine-induced stereotyped behavior.

Gabapentin, an antiepileptic drug, improves memory storage in mice

Male CF-1 mice were tested 48 h after training in a one-trial step-through inhibitory avoidance task. Immediately post-training i.p. injections of the antiepileptic drug gabapentin (1-aminomethyl cyclohexaneacetic acid) (GBP; 5, 10, 50, and 100 mg/kg) induced a dose-dependent enhancement of retention performance. Gabapentin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of GBP on retention were not due to non-specific proactive effects on response latencies. The effects of GBP (10 mg/kg) were time-dependent, and the administration of GBP (10 mg/kg) 30 min before training also enhanced retention performance. However, the administration of GBP (10 mg/kg) 30 min prior to the retention test did not modify retention latencies of mice that had received either saline or GBP (10 mg/kg) immediately after training. Altogether, the results suggest that GBP influences retention by modulating time-dependent processes involved in memory storage, although the mechanism(s) of this action remain to be established.

An in vitro model to evaluate the effect of an organophosphoric agropesticide on cell proliferation in mouse seminiferous tubules

Recently, there has been public concern about the toxic effects of organophosphoric pesticides (OP) upon human and animal populations. Since the seminiferous epithelium is an actively proliferating tissue, it was of interest to study germ cell proliferation in the isolated seminiferous tubules of mice that were cultured in the presence of Parathion or paraoxon, its metabolite. Eighteen 3-month-old CF-1 male mice were used. Paraoxon (PO) and Parathion (PT) were added to cultures of seminiferous tubules in the following groups: (1) Ham F-10 medium pH 7.4 (M) (control); groups 2 to 5, M + decreasing doses of either PO or PT (0.8; 0.4; 0.04; 0.004; 0.0004 mM). Each group consisted of six mice. Incubation of the tubules was carried out for 5 h at 35 degrees C, 5% CO2, 95% air. One hour before the end of incubation 5 microCi of 3H-thymidine was added to the cultures. DNA uptake was measured by scintillation counting. PO and PT at concentrations of 0.8 mM elicited a sharp decrease in testicular DNA synthesis. Recuperation at concentrations under 0.4 mM was different. With PO it was rapid, possibly due to the high detoxificative ability of the testis, which contains high quantities of the enzyme 'type A esterases' that hydrolyses PO. At concentrations lower than PO, PT has an inhibitory effect upon germ cell proliferation, which deserves further research.

Peroxynitrite Scavengers for the Acute Treatment of Traumatic Brain Injury

Recent evidence has suggested that the superoxide and nitric oxide-derived reactive oxygen species peroxynitrite (ONOO-) may play a significant role in the acute pathophysiology of brain injury. One pharmacological mechanism by which ONOO(-)-mediated damage might be interrupted is by the administration of scavenging compounds such as the thiol-containing compound penicillamine. In the present study, we examined the ability of either penicillamine (Pen) or the more brain penetrable penicillamine methyl ester (PenME) (0.01, 0.1, 1.0 or 10.0 mg/kg i.v. 5 min post-injury) to improve the early (1 hr) neurological recovery (grip score) of male CF-1 mice after a severe (900 g-cm; 50 g x 18 cm) injury. Pen produced a dose-related improvement in grip score. At 1.0 mg/kg, a +112% improvement was observed compared to vehicle-treated mice, and at 10.0 mg/kg, the increase was +168% (both, p < 0.05). PenME more potently improved the 1-hr grip score, but the magnitude of the optimal effect (+96% at 0.1 mg/kg; p < 0.02) was no greater than that observed with Pen, which largely remains in the cerebral microvasculature. These results are consistent with a role of ONOO- in acute head injury, but suggest that microvascular scavenging may be of primary therapeutic importance during the early post-traumatic period.

Sensitization of Stereotyped Behavior to Amphetamine Is Context and Response Dependent

The present study was designed to determine whether the environmental context in which amphetamine is administered plays a role in the development of sensitization to the stereotyped behavioral effects of amphetamine in mice. In male CF-1 mice, the dose–response curve for stereotyped behavior elicited by amphetamine was shifted 1.9-fold to the left 48 h after pretreatment with 14 mg/kg amphetamine. Behavioral sensitization only developed in mice that were pretreated in the same or a similar environment as that of the test environment. In addition, when mice were placed in an environment that attenuated the acute expression of stereotyped behavior elicited by the pretreatment dose of amphetamine, sensitization never developed. A further experiment showed that 96% of the mice that expressed stereotypy after the ED 50 pretreatment dose of 10 mg/kg amphetamine showed a stereotyped behavioral response to the lesser dose of 7 mg/kg 48 h later, indicating sensitization. In contrast, mice that did not express stereotypy after the ED 50 dose of amphetamine failed to show a significant stereotyped behavioral response to amphetamine challenge compared to vehicle-pretreated controls. Therefore, the results indicate that preexposure to a single high dose of amphetamine produces context- and response-dependent sensitization to amphetamine-induced stereotyped behavior.

EFFECTS OF LEAD ON THE MALE REPRODUCTIVE SYSTEM IN MICE

The effect of environmental lead on the male reproductive system has been a major area of concern for several years. Lead toxicity to the male reproductive system of sexually mature male CF-1 mice was investigated by administering two concentrations of lead (0.25% and 0.5%) via drinking water for 6 wk. The low lead dose significantly reduced the number of sperm within the epididymis, while the high dose reduced both the sperm count and percentage of motile sperm and increased the percentage of abnormal sperm within the epididymis. There was no significant effect on testis weight; however, the high-dose treatment significantly decreased the epididymis and seminal vesicle weights as well as overall body weight gain. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) levels were not affected by lead administration indicating that in adult male CF-1 mice, lead targets testicular spermatogenesis and sperm within the epididymis to produce reproductive toxicity rather than acting at other sites within the hypothalamic-pituitary-testicular axis.

Frequency of micronuclei in the blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation

Purpose: To investigate the extent of genetic damage in the peripheral blood and bone marrow cells of mice exposed to ultra-wideband electromagnetic radiation (UWBR). Materials and methods: CF-1 male mice were exposed to UWBR for 15min at an estimated whole-body average specific absorption rate of 37mWkg-1. Groups of untreated control and positive control mice injected with mitomycin C were also included in the study. After various treatments, half of the mice were killed at 18h, and the other half at 24h. Peripheral blood and bone marrow smears were examined to determine the extent of genotoxicity, as assessed by the presence of micronuclei (MN) in polychromatic erythrocytes (PCE). Results: The percentages of PCE and the incidence of MN per 2000 PCE in both tissues in mice killed at 18h were similar to the frequencies observed in mice terminated at 24h. There were no significant di erences in the percentage of PCE between control and the mice with or without UWBR exposure; the group mean values (standard deviation) were in the range of 3.1 0.14 to 3.2 0.23 in peripheral blood, and 49.0 3.56 to 52.3 4.02 in bone marrow. The mean incidence of MN per 2000 PCE in control and in mice with or without UWBR exposure ranged from 7.7 2.00 to 9.7 2.54 in peripheral blood and 7.4 2.32 to 10.0 3.27 in bone marrow. Pairwise comparison of the data did not reveal statistically significant di erences between the control and mice with or without UWBR exposure groups (excluding positive controls). Conclusion: Under the experimental conditions tested, there was no evidence for excess genotoxicity in peripheral blood or bone marrow cells of mice exposed to UWBR.

Androgens and Estrogens Modulate 5-HT 1A and 5-HT 1B Agonist Effects on Aggression

COLOGER-CLIFFORD, A., N. G. SIMON, M. L. RICHTER, S. SMOLUK AND S. LU. Androgens and estrogens modulate 5-HT 1A and 5-HT 1B agonist effects on aggression . PHYSIOL BEHAV 65(4/5) 823–828, 1999.—Intermale offensive aggressive behavior is facilitated by gonadal steroids and inhibited by serotonin (5-HT), presumably through its effects at 5-HT 1A and 5-HT 1B receptor sites. To examine the interaction between these neuroendocrine and neurochemical regulatory systems, CF-1 male mice were gonadectomized and implanted with silastic capsules containing either diethylstilbestrol (DES, a synthetic estrogen), the nonaromatizable androgens methyltrienolone (R1881) or dihydrotestosterone (DHT), or testosterone (T). Two weeks later, they were given 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT 1A agonist; 0.1 or 1.0 mg/kg), CGS12066B (a 5-HT 1B agonist; 4.0 or 8.0 mg/kg), 0.1 or 1.0 mg/kg 8-OH-DPAT + 4.0 mg/kg CGS12066B, or vehicle, and tested for aggression. In the presence of DES, the higher 8-OH-DPAT dose given in combination with CGS attenuated aggression in comparison to vehicle controls. When given nonaromatizable androgen (R1881 or DHT), all drug treatments except 0.1 mg/kg 8-OH-DPAT significantly reduced offensive attack behavior. In the presence of T, which provides estrogenic and androgenic stimulation, aggression scores were significantly reduced when males were given the high dose of 8-OH-DPAT or CGS12066B, as well as in the 1.0 mg/kg 8-OH-DPAT + CGS12066B condition. Assessments of changes in motor behavior showed significant impairment when 8.0 mg/kg CGS12066B was administered across all hormonal conditions, indicating that reductions in offensive aggression in these treatment groups were nonspecific. The results demonstrate differential effects of the steroidal environment on the ability of 5-HT 1A and 5-HT 1B agonists to modulate aggression, with estrogens producing a more restrictive environment than androgens for serotonergic inhibition of male-typical aggressive behavior.

Dominant lethal study of α-asarone in male mice

α-Asarone is a hypolipidaemic agent obtained from Guatteria gaumeri, a medical plant used in Mexico to treat hypercholesteraemia and cholelithiasis. α-Asarone has been shown to be hepatocarcinogenic and mutagenic in a human lymphocyte assay, a murine bone marrow cell assay and in an unscheduled DNA synthesis assay. In this study, α-asarone was tested for dominant lethal effects in male CF1 mice. The drug was given orally at doses of 0, 10 and 30 mg/kg per day for 5 days. Males were mated weekly with eight consecutive batches of naive, nulliparous female mice. Repeated matings revealed no perceptible effect of α-asarone on the incidence of pregnancy. Examination of surgically exposed uteri and ovaries of pregnant females on day 13–15 of gestation revealed an increased incidence of post-implantation loss. Semen examination of a separate group of mice showed a decreased concentration and motility of spermatozoa. These results suggest a dominant lethal mutation as well as direct α-asarone toxicity to spermatozoa by in treated mice.

Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation

LYTE, M., J. J. VARCOE AND M. T. BAILEY. Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. PHYSIOL BEHAV 65(1) 63–68, 1998.—Challenge of animals with infectious microorganisms is well documented to affect a number of behavioral measures through activation of immune-neural mechanisms. In the present study, the ability of an infectious microorganism to directly alter behavioral responses in the absence of an overt immunologic response was examined. Eight-week-old CF-1 male mice were infected orally with the Gram-negative pathogen Campylobacter jejuni in order to establish a subclinical infection that did not result in immune activation. Microbiological examination of cecal contents revealed the presence of C. jejuni in all infected, but not control, animals 1 and 2 days post-oral challenge. Measurement of interleukin-6 (IL-6) levels and peripheral blood leukocyte populations did not reveal the activation of an overt immune response in 1 or 2 day infected animals as compared to controls. Infected mice demonstrated altered levels of anxiety-like behaviors on the elevated plus-maze as compared to controls on Day 2, but not Day 1, as reflected by a significant decrease in exploratory and an increase in nonexploratory behaviors. The anxiogenic effect of a subclinical infection in the absence of an overt immunologic response suggests that the direct activation of neural pathways by microorganisms may play a role in behavior.

Protective effects of cruciferous seed meals and hulls against colon cancer in mice

Protective effects of diets containing cruciferous seed meals or hulls against chemically-induced colon tumors were examined in male CF1 mice. When commercial crambe meal, autolyzed crambe meal, crambe hulls, high glucosinolate rapeseed meal, or canola meal were fed as 12% of the diets of mice injected with 1,2-dimethylhydrazine, 25–80% of the animals developed colon tumors. Animals fed a soybean meal control diet had a 100% tumor rate. Data suggest that cruciferous seed meals may contain a number of compounds that can exert protective effects against tumor formation and growth.

Serotonin Agonist-Induced Decreases in Intermale Aggression Are Dependent on Brain Region and Receptor Subtype

COLOGER-CLIFFORD, A., N. G. SIMON, S.-F. LU AND S. A. SMOLUK. Serotonin agonist-induced decreases in intermale aggression are dependent on brain region and receptor subtype. PHARMACOL BIOCHEM BEHAV 58(2) 425–430, 1997.—Testosterone (T) and its androgenic and estrogenic metabolites modulate the ability of serotonin (5-HT) 1A and 5-HT 1B agonists to inhibit intermale aggressive behavior. This study tested whether the lateral septum (LS) and medial preoptic area (MPO), which are part of the neuroanatomical substrate for aggression and contain androgen, estrogen, 5-HT 1A and 5-HT 1B receptors, represent sites where these modulatory effects occur. Gonadectomized CF-1 male mice were given silastic implants containing diethylstilbestrol (DES, a synthetic estrogen) or dihydrotestosterone (DHT, a nonaromatizable androgen) and implanted bilaterally with guide cannula directed at the LS or MPO. They were microinjected with either CGS12066B, a 5-HT 1B agonist (400 μM LS, 200 μM MPO); 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), a 5-HT 1A agonist (10 μM LS, 5 μM MPO); or combined CGS + 8-OH-DPAT treatment and tested for aggression 15 min later. When microinjections were given in the LS, androgen-treated males exhibited significantly reduced attack behavior in response to CGS or to CGS + 8-OH-DPAT. The attack behavior of DES-treated males was not reduced by any of the treatments. In contrast, all agonist treatments decreased aggression when injected into the MPO in both hormone conditions. The findings demonstrate regional variation in the ability of androgens and estrogens to modulate 5-HT 1A- and 5-HT 1B-agonist mediated reductions in aggression.

Neuroendocrine–Bacterial Interactions in a Neurotoxin-Induced Model of Trauma

Background: The destruction of noradrenergic nerve cell innervation and resultant release of norepinephrine into the systemic circulation accompany severe tissue trauma. To examine whether destruction of noradrenergic neurons may directly influence the growth of indigenous bacteriain vivo,the selective noradrenergic neurotoxic agent 6-hydroxydopamine (6-OHDA) was employed in a murine model of trauma-induced norepinephrine release. Materials and methods: Following 6-OHDA administration, the cecums of 6- to 8-week-old male CF-1 mice were excised and examined for total bacterial counts and identification of bacterial species present in both the luminal space and intestinal wall. Lipopolysaccharide levels were also measured. Results: An increase of 3–5 logs in the total gram-negative population, most notablyEscherichia coli,compared to controls on a per gram equivalent basis was observed at 1 day post-6-OHDA. Neurotoxin-induced alterations in cecal flora were completely inhibited by the prior administration of the catecholamine uptake blocker desipramine hydrochloride, indicating the specificity of the effect being due to the released norepinephrine. Within 14 days following chemical sympathectomy, during which regeneration of noradrenergic neurons occurs, the cecal flora returned to the distribution observed in controls. Levels of lipopolysaccharide were not increased in either the luminal contents or cecal tissue at any of the time points. Conclusions: These results suggest that the destruction of noradrenergic neurons during trauma and consequent release of norepinephrine into the systemic circulation may influence thein vivogrowth of the indigenous bacterial population within the gastrointestinal system.

Strain and sex differences in the effect of enflurane and isoflurane on heme metabolism in mice

1. 1.The influence of strain and sex on the effect of enflurane and isoflurane administration on heme metabolism was investigated to identify the animal model which could best reproduce the biochemical signs of acute intermittent porphyria. 2. 2. Enflurane produced 35% and 80% increases in ALA-S activity only in CF1 male and female mice, respectively, whereas isoflurane induced 40% enzyme activity in CF1 male. 3. 3. CF1 males showed around 35% decrease in blood PBGase and PBG-deaminase after administration of enflurane, whereas isoflurane provoked a striking inhibition (70%) in males of the C57 strain. 4. 4. Enflurane produced alterations in heme synthesis, which would fit a model of acute porphyria in CF1 male mice. On the other hand, isoflurane would mimic biochemical alterations of this porphyria in C57 males.