Strain differences of mice in learning of swimming behavior and effect of hemicholinium and vasopressin. Observation by a simple water maze apparatus]

In order to determine the strain differences in learning of swimming behavior and to study the influence of vasopressin or its derivatives on hemicholinium-3-induced impairment of water maze learning in mice, we designed a new apparatus using water maze which has three panels in small fish breeding water bath (L60 x W30 x H36 cm). In the first swimming, six strains of adult male mice, ICR, ddY, ddN, C3H/He, BALB/C and C57BL were subjected to learn swimming behavior twice a day for 6 d in a straight course. Only ICR, ddN, C57BL and BALB/C strain mice were chosen for the next experiment. In the second swimming, mice (ICR, ddN, C57BL, BALB/C) were swum in the water maze apparatus. Scopolamine-induced impairment of water maze learning was produced only in ICR, BALB/C mice, but not in C57BL and ddN strain, which was recovered by physostigmine. Amnesia was not obtained by intracerebroventricular injection (i.c.v.) of cycloheximide and AlCl3 in mice (ICR). Hemicholinium-induced amnesia was improved by vasopressin and desmopressin. Lysine-vasopressin and oxytocin were without affecting hemicholinium-induced amnesia. Pretreatment with a vasopressin antagonist, ([1-(beta-mercapto-beta,beta-cyclopenta-methylene propionic acid), 2-(o-methyl)tyrosine arginine]-vasopressin) resulted in a reversible effect on the improvement of hemicholinium-induced amnesia by vasopressin. Of four different strain mice, ICR mice were the most preferable to the presently used test. They were also more responsive to hemicholinium and vasopressin than the other strains. These results suggest that the simple water maze apparatus may be useful for a pre-examination of nootropics or a study of learning of swimming behavior in mice.     

Histamine-releasing properties of mast cells from various strains of mice

A comparison has been made of the in vitro histamine releasing capacity of peritoneal mast cells from BALB/c, C3H/A, C57BL/6J and CFW mouse strains in response to immunological and non-immunological stimuli namely anti-mouse IgE, Concanavalin A (Con A), ionophore A23187 and sodium fluoride. Anti-IgE-induced histamine secretion was highest in mast cells of CFW mice, intermediate in the cells of C57BL/6J and C3H/A mice and lowest in the cells of BALB/c mice. Similar, although less pronounced, strain-dependent differences were observed in Con A-induced release. Mast cells of C57BL/6J and CFW mice were significantly more sensitive to the action of ionophore A23187 compared to the two other strains, although the cells of each strain responded in different manner. Sodium fluoride-induced histamine release occurred in two ways: from mast cells of BALB/c and C57BL/6J it was dose-dependent at NaF concentrations of 1-15 mM, whereas cells of the two other strains were insensitive to the action of NaF at concentrations of 1-5 mM but at a concentration of 7.5 mM, a very strong potentiation of release was observed. Our results suggest functional heterogeneity of mast cells from various strains of mice, a point to be considered in further studies of mast cell function.     

Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c,C57BL/6, and DBA/2 mice

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of righting reflex was, however, differentially affected in all three strains by naltrexone. The BALB mice affected in all three strains by naltrexone. The BALB mice were the most sensitive strain (1 mg/kg naltrexone significantly counteracted ethanol hypnosis), the C57BL mice were intermediate (8 mg/kg naltrexone required to antagonize this effect of ethanol), and the DBA mice were least sensitive (no effect evident even at the highest dose of 8 mg/kg) to naltrexone. Thus, naltrexone could antagonize the behavioral effects of a low and high dose of ethanol, but the three strains, which differ in their behavioral response to ethanol, also were differentially sensitive to the effect of naltrexone in reversing ethanol-induced hypnosis and ethanol-induced changes in locomotor activity.     

Psychomotor stimulant effects of cocaine in rats and 15 mouse strains

Relative to intravenous drug self-administration, locomotor activity is easier to measure with high throughput, particularly in mice. Therefore its potential to predict differences in self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) is appealing, but such predictive value is unverified. The main goal of this study was to evaluate the utility of the locomotor assay for accurately predicting differences in cocaine self-administration. A second goal was to evaluate any correlation between activity in a novel environment, and cocaine-induced hyperactivity, between strains. We evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but BALB/cJ mice showed locomotor habituation and significant cocaine-induced hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine self-administration. As previously reported, female rats showed greater cocaine-induced locomotion than males, but this was only observed in one of 15 mouse strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ, BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some correlation between all-or-none locomotion in a novel environment, and stimulant and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced activity offered a clear prediction of relative reinforcing effects among strains. Additionally, these results should aid in selecting mouse strains for future studies in which relative locomotor responsiveness to psychostimulants is a necessary consideration.     

Dose-response relationships of hepatic acyl-CoA oxidase and catalase activity and liver mitogenesis induced by the peroxisome proliferator ciprofibrate in C57BL/6N and BALB/c mice.

The dose-response for key hepatic effects of the peroxisome proliferator ciprofibrate, 2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2- methylpropanoic acid, was delineated in mice and strain differences in response were demonstrated. Ciprofibrate was fed at concentrations ranging from 0.1 to 250 ppm to male C57BL/6N and BALB/c mice and the induction of hepatic acyl-CoA oxidase and catalase, peroxisomal enzymes involved in the formation and degradation of hydrogen peroxide, and liver hepatomegaly and mitogenesis were measured. No effect was found for enzyme induction at 5.0 ppm or less in either strain. Likewise, hepatomegaly was not found at 5.0 ppm, but mitogenesis was observed in BALB/c mice at 1.0 ppm. C57BL/6N mice demonstrated greater basal and postexposure acyl-CoA oxidase activity than BALB/c mice, while BALB/c mice demonstrated greater catalase activity and induction of liver mitogenesis. The threshold exposure level for induction of acyl-CoA oxidase activity was approximately the same as that for induction of mitogenesis in C57BL/6N mice; in contrast, the threshold exposure level for induction of acyl-CoA oxidase activity was at least one order of magnitude greater than that required for induction of mitogenesis in BALB/c mice. Thus, the induction of the peroxisomal enzyme involved in the formation of hydrogen peroxide and increased mitogenesis are not mechanistically linked. The differential effects observed in the two mouse strains provide the basis for development of a quantitative model of peroxisome proliferator-induced carcinogenicity in which cellular effects can be related to carcinogenicity.     

Differential stress-induced alterations in tryptophan hydroxylase activity and serotonin turnover in two inbred mouse strains

Chronic stress and alterations in the serotonergic system are key predisposing factors to the development of major depression. Tryptophan hydroxylase (TPH) is the key enzyme in the biosynthesis of serotonin (5-HT). The effects of chronic stress on TPH activity remain uncertain. The BALB/c strain is stress-sensitive, highly anxious and possess a single nucleotide polymorphism in their tryptophan hydroxylase (TPH) 2 gene (tph2), resulting in reduced levels of central serotonin compared to C57BL/6J mice, which harbour the wild-type allele. We examined the effects of repeated restraint stress on the serotonergic system and TPH activity in these two inbred strains. TPH activity was assessed by accumulation of 5-hydroxytryptophan, a rapidly decarboxylated intermediate metabolite of tryptophan and precursor of 5-HT, using an enzyme inhibition strategy. Furthermore, the concentrations of 5-HT and its major metabolite 5-hydroxy indole acetic acid were assessed. Interestingly, 5-HT turnover was significantly increased in the majority of the brain regions assessed following acute stress in C57BL/6J. In contrast, BALB/c mice exhibit significant increases in 5-HT turnover in the striatum and hippocampus only following repeated stress. On the other hand, TPH activity was significantly decreased in the brainstem and cortical regions of C57BL/6J mice following both acute and chronic stress. Conversely, no significant stress-induced change in BALB/c TPH activity was observed. Together these data highlight the differential serotonergic response of BALB/c and C57BL/6J mice to acute and chronic restraint stress and may offer insight into the observed differences in their stress-related phenotypes.     

Accelerated differentiation of bone marrow-derived dendritic cells in atopic prone mice

NC/Nga mice are atopic prone mice that can be an animal model for human atopic dermatitis (AD). Dendritic cells (DC) as professional antigen-presenting cells (APC) are the most capable inducers of immune responses. The present study using BALB/c, C57BL/6J, and NC/Nga male mice investigated whether differentiation and function of DC were associated with atopic prone. Bone marrow-derived DC (BMDC) were differentiated by culture with granulocyte macrophage colony stimulating factor (GM-CSF). At days 0, 6, and 8 of culture with GM-CSF, the expression of MHC class II, co-stimulatory molecules (CD80, CD86), and of DC markers (CD11c, DEC205) was measured by flow cytometry. Antigen-presenting activity of BMDC and cytokine production were measured by ELISA. The cell numbers and the expression of MHC class II, co-stimulatory molecules, and of DC markers on BMDC from NC/Nga mice were significantly larger than those from BALB/c and C57BL/6J mice. Antigen-presenting activity of BMDC was significantly greater in NC/Nga and C57BL/6J mice than in BALB/c mice. BMDC-stimulated IFN-gamma production from T-cells was significantly lower in NC/Nga or BALB/c mice than in C57BL/6J mice, whereas IL-4 production was significantly greater in NC/Nga and C57BL/6J mice than in BALB/c mice. Taken together, GM-CSF-stimulated differentiation of BMDC was more accelerated in atopic prone NC/Nga mice than in the other strains of mice. The enhancement of differentiation and function of DC caused by genetic background may be related, at least partly, to the induction or aggravation of allergic/atopic diseases.     

Locomotor reactivity to a novel environment and sensitivity to MK-801 in five strains of mice

The ability of a noncompetitive antagonist of the N-methyl-D-aspartate receptor, MK-801, to stimulate locomotor activity (LMA) in mice was compared across CD-1, MF1, NIH Swiss (NIHS), C57BL6/J and BALB/C strains with the aim of identifying the most suitable strain for a putative model of schizophrenia. Animals were habituated to novel LMA cages for 1 h before receiving either saline or MK-801 (0.1, 0.32, or 0.5 mg/kg; i.p.) and activity recorded for 2 h. At the end of the test, blood and brain samples were taken and the total concentrations of MK-801 determined. Mice strains differed in habituation; C57BL6/J mice were the most active, whereas BALB/C mice were the least active and slowest to habituate. Robust strain-dependent differences in sensitivity to MK-801 were found, but not to saline. NIHS, C57BL6/J and BALB/C were more active in response to MK-801, exhibiting more rapid, robust and long-lasting increases in LMA than CD-1 or MF1 mice. Total concentrations of MK-801 in the brain did not differ across the strains. We found no correlation between the LMA stimulated by novelty and MK-801. NIHS, C57BL6/J and BALB/C appeared significantly more sensitive to MK-801 than CD-1 and MF1 and can be strains of choice in evaluating the effect of antipsychotic compounds in this model.     

Differences in acquisition of discrete lever-press and shuttle avoidance responses in 6 strains of mice

Characteristics of the acquisition processes of discrete lever-press and shuttle avoidance responses (intertrial interval = 25 sec, warning duration = 5 sec with an escape contingency, and 1 session = 1 hr training/day) as well as those of the ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB/c, C57BL/6, C3H/He and DBA/2). In the lever-press avoidance situation, the dd, BALB/c and DBA/2 strains demonstrated a good avoidance response, showing average avoidance rates of higher than 80% within 10-15 sessions of the training. The C3H/He also demonstrated a good avoidance response, though 20 sessions or more of the training were required to attain to the level. The ICR and C57BL/6 strains demonstrated a poorer avoidance response than the other 4 strains, and achieved average avoidance rates of 30-40%. The dd, BALB/c, C3H/He and DBA/2 strains also demonstrated a good shuttle avoidance response when they were trained in an experimental box of 50 cm in width. In contrast, the ICR and C57BL/6 strains demonstrated an extremely poor avoidance response in this situation, showing an average avoidance rate of less than 10%. However, when the dd, ICR and C57BL/6 strains were trained in a shuttle box of 30 cm in width, they rapidly acquired the avoidance response, and the average avoidance rates finally achieved were much higher than those of the mice trained in the shuttle box of 50 cm in width. In particular, the C57BL/6 strain exhibited the best avoidance response among the 3 strains. The ambulatory activity of the C57BL/6 strain was less than those of the other 5 strains.     

Effects of d-amphetamine and scopolamine on activity before and after shock in three mouse strains.

In three experiments the following results were obtained: (a) Activity was greater both prior to and following exposure to shock among C57BL/6J mice than in DBA/2J mice, which in turn was greater than that of A/J mice. (b) Scopolamine hydrobromide increased general activity in DBA/2 and A mice, but had either no effect or decreased activity in the C57BL/6 strain. Following exposure to shock, however, the disinhibitory effects of scopolamine were apparent in all three strains. (c) d-amphetamine increased activity in all three strains. Moreover, following the single shock d-amphetamine had excitatory effects among both A and DBA/2 mice such that activity exceeded the level observed with d-amphetamine alone. Following several shock presentations a small but significant excitation was observed in C57BL/6 mice as well. Data were interpreted in terms of disinhibitory and excitatory effects of scopolamine and d-amphetamine, respectively, as well as possible interactions between the catecholaminergic and cholinergic systems. In addition, implications for sources of strain differences in avoidance behavior are discussed.     

Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours.Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion.In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p < 0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p < 0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p < 0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p < 0.001) and the spent time in the centre (p < 0.05).In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p < 0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p < 0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p < 0.05).A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses.     

Role of endogenous enkephalins in locomotion and nociception studied with peptidase inhibitors in two inbred strains of mice (C57BL/6J and DBA/2J)

Acetorphan, a parenterally active enkephalinase inhibitor, induced dose-dependently a naloxone-reversible analgesia on the hot-plate jump test in DBA/2J (DBA2) mice but was devoid of effects in C57BL/6J (C57) mice. By contrast, acetorphan increased locomotion in both strains; however, the DBA2 strain was much more sensitive than C57 mice to the locomotor stimulant effect. The increased locomotion was antagonized by naloxone in both strains. These data suggest that endogenous enkephalins modulate nociception and locomotion in the two inbred strains differently.     

Genetic variation of basal iron status, ferritin and iron regulatory protein in mice: potential for modulation of oxidative stress

Toxic and carcinogenic free radical processes induced by drugs and other chemicals are probably modulated by the participation of available iron. To see whether endogenous iron was genetically variable in normal mice, the common strains C57BL/10ScSn, C57BL/6J, BALB/c, DBA/2, and SWR were examined for major differences in their hepatic non-heme iron contents. Levels in SWR mice were 3- to 5-fold higher than in the two C57BL strains, with intermediate levels in DBA/2 and BALB/c mice. Concentrations in kidney, lung, and especially spleen of SWR mice were also greater than those in C57BL mice. Non-denaturing PAGE of hepatic ferritin from all strains showed a major holoferritin band at approximately 600 kDa, with SWR mice having > 3-fold higher levels than C57BL strains. SDS PAGE showed a band of 22 kDa, mainly representing L-ferritin subunits. A trace of a subunit at 18 kDa was also detected in ferritin from SWR mice. The 18 kDa subunit and a 500 kDa holoferritin from which it originates were observed in all strains after parenteral iron overload, and there was no major variation in ferritin patterns. Although iron uptake studies showed no evidence for differential duodenal absorption between strains to explain the variation in basal iron levels, acquisition of absorbed iron by the liver was significantly higher in SWR mice than C57BL/6J. As with iron and ferritin contents, total iron regulatory protein (IRP-1) binding capacity for mRNA iron responsive element (IRE) and actual IRE/IRP binding in the liver were significantly greater in SWR than C57BL/6J mice. Cytosolic aconitase activity, representing unbound IRP-1, tended to be lower in the former strain. SWR mice were more susceptible than C57BL/10ScSn mice to the toxic action of diquat, which is thought to involve iron catalysis. If extrapolated to humans, the findings could suggest that some people might have the propensity for greater basal hepatic iron stores than others, which might make them more susceptible to iron-catalysed toxicity caused by oxidants.     

Characteristics of effects of repeated scopolamine administration on ambulatory activity in mice and methamphetamine sensitivity in the scopolamine-experienced mice: comparison among 6 strains

Effects of scopolamine (0.5 mg/kg, s.c.) on ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB, C57BL, C3H and DBA). Scopolamine increased ambulatory activity, and the sensitivities were in the order of ICR greater than C3H greater than BALB greater than DBA greater than C57BL greater than dd. This was different from that produced by methamphetamine (2 mg/kg, s.c.) where the order was ICR greater than dd greater than DBA greater than C3H greater than C57BL greater than BALB. A tolerance to the ambulation-increasing effect of scopolamine was progressively produced in dd, ICR, C57BL and DBA strains, but not in BALB and C3H strains, when the drug was administered 5 times at intervals of 3-4 days. The repeated scopolamine treatment elicited a major enhancement of the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) in BALB and C3H strains and a minor enhancement in the C57BL strain, whereas dd, ICR and DBA strains did not exhibit a marked change in the sensitivity to methamphetamine even after the same treatment with scopolamine. These results suggest that the ambulation-increasing effect of scopolamine is different from that of methamphetamine and that the interaction between scopolamine and methamphetamine varies among different strains of mice.     

Genetic differences in the locomotor response to single and daily doses of phencyclidine in inbred mouse strains

Genetic differences in the locomotor stimulant effects of both single and daily administration of phencyclidine were investigated in four inbred strains of male mice A/J, C57BL/6J, C57BL/6ByJ and BALB/cByJ. Each mouse was injected i.p. once in Experiment 1, or daily for 5 or 11 days in Experiments 2, 3 and 4. Locomotor activity was assessed with an automated photoelectric system. Significant strain differences were found in the response to a single as well as repeated doses of phencyclidine. A/J mice showed the greatest initial response to phencyclidine and developed tolerance to daily phencyclidine. C57BL/6ByJ mice showed initial resistance to acute phencyclidine, but developed sensitization to daily phencyclidine. The responses of both C57BL/6J and BALB/cByJ mice to acute phencyclidine were low to moderate, and did not change significantly following daily phencyclidine. The results of this study indicate that different genetic mechanisms are involved in responses to single and daily injections of phencyclidine.     

Reverse tolerance to ambulation-increasing effects of methamphetamine and morphine in 6 mouse strains

Effects of single administration of methamphetamine (1, 2 and 4 mg/kg, s.c.) and morphine (5, 10 and 20 mg/kg, s.c.) and repeated administration of methamphetamine (2 mg/kg, s.c.) and morphine (10 mg/kg, s.c.) on ambulatory activity were investigated in 6 mouse strains: dd, ICR, BALB/c, C57BL/6, C3H/He and DBA/2. Although there were differences in the drug sensitivities among mouse strains, methamphetamine and morphine increased the ambulatory activity in all the strains except for the DBA/2 strain that showed an increase only after morphine. Repeated 5 times administration of methamphetamine at intervals of 3-4 days induced a reverse tolerance (an enhancement in the sensitivity) to the ambulation-increasing effect in all the strains with a marked degree in dd, ICR, C3H/He and DBA/2 strains and a slight degree in BALB/c and C57BL/6 strains. The same treatment with morphine induced reverse tolerance to the effect of morphine markedly in C57BL/6 and C3H/He strains and moderately in dd, ICR and BALB/c strains, but the DBA/2 strain showed no significant change in the ambulatory activity throughout the repeated 5 times administration of morphine. There was positive correlation between the initial drug sensitivities of animals and the degrees of the reverse tolerance in either methamphetamine or morphine. Furthermore, the reverse tolerance to methamphetamine and morphine was sometimes transferable, although such cross interaction varied among mouse strains.     

Biodisposition of theophylline. II. Effect of aromatic hydrocarbon treatment in mice

The effect of polycyclic aromatic hydrocarbons on theophylline clearance was examined in six inbred mice strains. The DBA/2 and SJL strains were nonresponsive to this treatment, whereas C3H/HeJ, C57BL/6, BALB/c, and A/J strains were responsive. In the responsive strains, the total body clearance increased by a factor of 2.3 to 3.4, apparently due to a general induction of all metabolic pathways. The production of 1,3-dimethyluric acid was not increased in the C57BL/6 strain. The variation in induction among responsive strains appeared to be primarily associated with the increase in the oxidation to 1,3-dimethyluric acid.     

Differential antidepressant-like response to lithium treatment between mouse strains: effects of sex, maternal care, and mixed genetic background

Background

Lithium is a mood stabilizer with both antidepressant and antimanic properties, however its mechanism of action is unclear. Identifying the genetic factors that influence lithium’s therapeutic actions will be an important step to assist in identifying such mechanisms. We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain.

Objectives

This study aimed to assess the roles of both genetic and non-genetic factors such as sex and non-shared environmental conditions that may mediate differential behavioral responses to lithium.

Methods

Mice were treated with lithium for 10 days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal. We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains.

Results

Neither sex nor maternal care significantly influenced the differential antidepressant-like response to lithium. Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain but had no effects in BALB/cJ mice. Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain.

Conclusions

Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains. Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium’s therapeutic actions.     

Behavioral effects of trimethyltin in two strains of mice. I. Spontaneous motor activity

Adult male mice (C57BL/6N and BALB/c) were administered single doses of trimethyltin X Cl (TMT) by the ip route. The effects of TMT administration were determined on lethality (3-6 mg/kg), spontaneous motor activity (SMA), and the physical appearance of the mice (0.3-3 mg/kg). The effects of TMT on lethality were strain dependent in that a single dose of 3 mg/kg, ip, produced approximately 35% lethality in the C57BL/6N strain during the first 72 hr following administration. Less than 15% lethality was observed at this dose in the BALB/c strain. In both strains, 3.5 mg/kg, ip, produced more than 70% lethality during the first 144 hr after administration. Higher doses produced proportionally greater lethality. The SMA of both strains was not affected significantly at doses below 1 mg/kg, ip. At 1 mg/kg a small decrease in activity was observed during the first 24 hr. At 3 mg/kg, SMA was initially decreased in both strains. However, the decrease was of smaller magnitude in the C57BL strain and was followed by a large increase in SMA which did not return to control levels for approximately 1 week. An increase in SMA was observed in the BALB/c strain on the fifth day following TMT but returned to control values by Day 6. At 3 mg/kg, ip, the C57BL mice were observed to have severe whole body tremors and were hypersensitive to external stimuli. The whole body tremor was not as marked in the BALB/c strain. Neuropathological studies on the treated mice indicated that the behavioral studies paralleled the pathology produced by TMT. These data confirm the initial observation of greater sensitivity of the mouse to toxic effects of TMT compared to the rat.