Immobility stress induces depression-like behavior in the forced swim test in mice: effect of magnesium and imipramine

Previously, we demonstrated antidepressant-like effect of magnesium (Mg) in the forced swim test (FST). Moreover, the joint administration of Mg and imipramine (IMI) at ineffective doses per se, resulted in a potent reduction in the immobility time in this test. In the present study, we examined the effect of immobility stress (IS), and Mg and/or IMI administration on FST behavior. IS induced enhancement of immobility time, which was reversed by Mg or IMI at doses ineffective in non-stressed mice (10 mg/kg and 15 mg/kg, respectively). The joint administration of Mg and IMI was effective in both IS and non-stressed animals in FST. IS did not significantly alter locomotor activity, while IMI or Mg + IMI treatment in IS mice reduced this activity. We also measured serum and brain Mg, IMI and its metabolite desipramine (DMI) concentration in mice subjected to FST and injected with Mg + IMI, both restrained and non-restrained. In the present study we demonstrated a significant increase (by 68%) in the brain IMI and a slight, non-significant reduction in DMI concentration in IS + Mg + IMI + FST vs. Mg + IMI + FST groups, which might indicate the reduction in brain IMI metabolism. The IS-induced reduction in brain IMI metabolism did not participate in the activity in FST, since no differences in such activity were noticed between IS + Mg + IMI + FST and Mg + IMI + FST groups. The present data suggest that IS-induced increase in immobility time in FST is more sensitive for detection antidepressant-like activity. However, further studies are needed to examine the effect of other antidepressants in such an experimental paradigm.     

NMDA/glutamate mechanism of antidepressant-like action of magnesium in forced swim test in mice

Antidepressant-like activity of magnesium in forced swim test (FST) was demonstrated previously. Also, enhancement of such activity by joint administration of magnesium and antidepressants was shown. However, the mechanism(s) involved in such activity remain to be established. In the present study we examined the involvement of NMDA/glutamate pathway in the magnesium activity in FST in mice. In the present study we investigated the effect of NMDA agonists on magnesium-induced activity in FST and the influence of NMDA antagonists with sub-effective doses of magnesium in this test. Magnesium-induced antidepressant-like activity was antagonized by N-methyl-d-aspartic acid (NMDA). Moreover, low, ineffective doses of NMDA antagonists (CGP 37849, L-701,324, d-cycloserine, and MK-801) administered together with low and ineffective doses of magnesium exhibit significant reduction of immobility time in FST. The active in FST doses of examined agents did not alter the locomotor activity (with an exception of increased activity induced by MK-801). The present study indicates the involvement of NMDA/glutamate pathway in the antidepressant-like activity of magnesium in mouse FST and further suggests antidepressant properties of magnesium.     

Effects of combined treatment with imipramine and metyrapone in the forced swimming test in rats. Behavioral and pharmacokinetic studies

In the present study, we examined the effects of imipramine (IMI) and metyrapone (MET) given alone or in combination of IMI and MET in the forced swimming test in rats. We also measured pharmacokinetic parameters: the level of IMI and its metabolite, desipramine (DMI), in the rat plasma and brain (1 h after the forced swimming test). The present studies indicate that MET (50 mg/kg) reduced immobility time. Combined treatment with MET (50 mg/kg) and IMI (5 or 10 mg/kg) produced stronger antidepressant-like effect than either of drugs given alone. Sulpiride (dopamine D2/3 antagonist), or WAY 100635 (5-HT1A antagonist) but not prazosin, (alpha1-adrenergic antagonist), at doses ineffective in the forced swimming test, inhibited an antidepressant-like effect induced by co-administration of IMI with MET. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and MET failed to alter the locomotor activity of rats, measured in the open field test. MET elevated the concentrations of IMI and DMI in plasma, and the total drug concentration (IMI + DMI) was doubled by MET. In the brain, MET enhanced the concentration of IMI, but decreased that of DMI, consequently, the brain IMI/DMI ratio increased twice. The total drug concentration in the brain (IMI + DMI) was not changed significantly by MET treatment. The obtained results suggest that dopamine D2/3 and 5-HT1A receptors may contribute to the mechanism of synergistic action of IMI and MET in the forced swimming test in rats, and that pharmacokinetic interaction should not have a substantial impact on the MET-induced potentiation of IMI effect, observed in vivo. These findings may be of particular importance to pharmacotherapy of drug-resistant depression.     

Effects of acute and chronic treatment with magnesium in the forced swim test in rats

The antidepressant-like activity of magnesium, the non-specific N-methyl-D-aspartate glutamate receptor antagonist, in the mice forced swim test was demonstrated previously. In the present study, the effects of this biometal were studied in the rat forced swim test. Magnesium (MgCl2) at doses ranging from 15 to 50 mg Mg/kg reduced the immobility time in the forced swim test, thus exerting antidepressant-like activity. To evaluate tolerance to this effect, we also performed experiments with the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments (S + S), chronic saline and magnesium challenge (S + Mg), chronic magnesium and saline challenge (Mg + S), chronic magnesium and magnesium challenge (Mg + Mg). The antidepressant-like effect of magnesium was demonstrated in the group treated acutely with magnesium (S + Mg) but not in the chronically treated group (Mg + S) and (Mg + Mg). It is interesting to note that in Mg + Mg group serum concentration of magnesium was quite similar to the S + Mg group (6.44 vs. 6.08 mg/100 ml, respectively), which displayed antidepressant-like effect. The results confirmed that magnesium administered acutely induced the antidepressant-like effects also in rats. However, contrary to mice, chronic treatment with magnesium induced tolerance to this effect in rats.     

Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies

Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptor, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either of drugs given alone. Since it has been suggested that, in addition to their other functions, dopamine and alpha(1)-adrenergic receptors may play a role in behavioral response in the forced swimming test, in the present study we examined the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in combination with IMI in the forced swimming test in rats. We also measured the level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA (20 mg/kg) produced stronger antidepressant-like effect than either of agents given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the forced swimming test) inhibited an antidepressant-like effect induced by co-administration of IMI and AMA. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and AMA failed to enhance the locomotor activity of rats, measured in the open field test. Also sulpiride and prazosin did not decrease the exploratory activity induced by co-administration of IMI and AMA. The above result suggests that the dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism of synergistic action of IMI and AMA in the forced swimming test in rats. The pharmacokinetic interaction can be excluded, since AMA did not change significantly the antidepressant level in the rat plasma and brain, measured 1 h after exposure to the forced swimming test.     

Influence of the phosphodiesterase type 5 inhibitor, sildenafil, on antidepressant-like activity of magnesium in the forced swim test in mice

Magnesium, which acts as an antagonist of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, exerts antidepressant-like activity in animal models of depression. The present study was undertaken to elucidate the influence of sildenafil, a phosphodiesterase type 5 inhibitor, on the anti-immobility action of magnesium in the forced swim test in mice. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of the behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. Serum and brain magnesium levels were assayed spectrophotometrically. Magnesium at a dose of 30 mg/kg, i.p. significantly decreased the immobility time while sildenafil (5, 10 and 20 mg/kg, i.p.) in a dose-dependent manner reduced the antidepressant-like activity of magnesium. The co-administration of magnesium with sildenafil at the highest dose entirely abolished the antidepressant-like effect of magnesium and caused a statistically significant increase in immobility duration as compared to the control group. Combination of magnesium with sildenafil resulted in a potent reduction (80%) of locomotor activity and pharmacokinetic studies showed a significant increase of magnesium concentration in serum (as compared to magnesium treatment alone) without changes within brain tissue in mice treated with magnesium and sildenafil. When given alone, sildenafil caused a significant increase in magnesium levels in both serum and brain. Our results indicate that a simultaneous treatment with magnesium and sildenafil results in hypermagnesemia in laboratory animals. However, the mechanism underlying this effect remains elusive.     

Influence of acute or chronic administration of ovarian hormones on the effects of desipramine in the forced swim test in female rats

Rationale

Gender may influence antidepressant (AD) treatment outcome. In order to address this preclinically, the potential effects of ovarian hormones on AD treatment in ovariectomized female rats were investigated.

Objectives

In the first study, the effect of acute administration of estrogen and progesterone on the antidepressant-like effects of desipramine (DMI), a selective norepinephrine reuptake inhibitor (SNRI), was investigated in the forced swimming test (FST). In the second study, the effect of chronic administration of these hormones on the effects of chronically administered DMI was investigated.

Results

In the acute study, the hormones blocked the effects of DMI in the FST as demonstrated by the absence of either a reduction in immobility or an increase in climbing behavior in animals treated with DMI in combination with the hormones. Concentration-response experiments on hippocampal synaptosomes revealed no changes in the Km or Bmax for uptake of ³H-NE in hormone-treated rats. In the chronic study, the antidepressant-like effects of DMI in the FST were not blocked by chronic administration of hormones. Interestingly, the hormones affected the serum concentrations of DMI. These levels were significantly higher in animals receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with placebo.

Conclusions

Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations).     

Pharmacokinetics of imipramine after single and multiple intravenous administration in rats

Plasma and brain levels of imipramine (IMI) and desmethylimipramine (DMI) in rats after single and multiple iv administration were estimated. IMI accumulated only in plasma, while DMI accumulated in plasma and brain of rats. The brain level of IMI and DMI was higher than plasma level. After multiple administration plasma DMI concentration was significantly greater than IMI concentration. It seems that IMI was obtained steady-state plasma concentration already at fifth day of multiple administration. High dose of IMI (10 mg/kg) caused that the relationship between steady-state concentration and dose of IMI cannot be expressed as a linear function.     

Antidepressant- and anxiolytic-like activity of magnesium in mice

The antidepressant- and anxiolytic-like effects of magnesium, an N-methyl-d-aspartate (NMDA) glutamate receptor inhibitor, were studied in mice using the forced swim test and elevated plus-maze test, respectively. The doses of 20 and 30 mg Mg/kg, reduced immobility time in the forced swim test exerting antidepressant-like activity. In the elevated plus-maze test, magnesium at the same doses produced anxiolytic-like effect. The doses of magnesium active in both tests did not affect locomotor activity. To evaluate the tolerance to these effects, we also performed experiments on the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments or serum magnesium determination (S+S), chronic saline and magnesium challenge (S+Mg), chronic magnesium and saline challenge (Mg+S), chronic magnesium and magnesium challenge (Mg+Mg). The antidepressant- and anxiolytic-like effect of magnesium was demonstrated in groups treated acutely and chronically with magnesium (Mg+Mg), but not in the Mg+S group. Moreover, these effects seem to be connected with at least 58% increase in serum magnesium concentration. The results indicate that magnesium induces the antidepressant- and anxiolytic-like effects without tolerance to these activities, which suggests a potential antidepressant and anxiolytic activity of magnesium in these disorders in humans.     

Lack of persistent effects of ketamine in rodent models of depression

RATIONALE: We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity. MATERIALS AND METHODS: One week after a single administration of ketamine (50-160 mg/kg), otherwise experimentally naive rats and mice were tested either in the forced swim test (FST) or the tail suspension test (TST). Other mice were also tested twice in the FST: immediately and 2 weeks after a single dose (1.25-50 mg/kg) of ketamine. In the next series of experiments, rats treated for 2 weeks twice daily with ketamine (50 or 160 mg/kg) or desipramine (10 mg/kg) were challenged with apomorphine and scored for locomotor activity and assayed for the density of cortical beta-adrenoceptors. The latter test was also carried out in rats that had received a single dose of ketamine (50 mg/kg) 1 week before the assay. The antidepressant-like (FST) and locomotor effects of ketamine (50 mg/kg) and desipramine (10 mg/kg) were assessed after their chronic (2 weeks, twice daily) administration as well. RESULTS: We report the lack of enduring antidepressant-like effect of ketamine in both rats and mice. A 2-week treatment with ketamine neither changed apomorphine-evoked locomotor hyperactivity nor did it decrease the density of cortical beta-adrenoceptors. However, some tolerance to the antidepressant-like effect of ketamine was noted in the FST, but it was accompanied by sensitization to its locomotor stimulatory effects. CONCLUSIONS: These data indicate that ketamine neither produces enduring antidepressant-like effects in rodents nor does it display antidepressant-like behavioral or neurochemical effects after chronic treatment.     

NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice

It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine.     

The effect of neuroleptics on imipramine demethylation in rat liver microsomes and imipramine and desipramine level in the rat brain

A study of the cytochrome P-450 level and imipramine (IMI) demethylase activity in liver microsomes of rats treated concurrently with IMI and chlorpromazine (CPZ) or IMI and chlorprothixene (CPX) for two weeks were carried out. Concomitant administration of IMI and CPZ or IMI and CPX elevated the cytochrome P-450 level and accelerated IMI demethylation in in vitro study. Kinetic study of IMI demethylation carried out in the absence or in the presence of CPZ or CPX revealed that those neuroleptics inhibited IMI demethylation via competitive mechanism. Simultaneously with the enzymatic study the brain level of IMI and its demethylated metabolite desipramine (DMI) was assessed. It was found that 1 hr after withdrawal of IMI and CPZ or IMI and CPX the brain level of IMI was elevated in comparison with that of IMI treated animals, and the ratio between DMI/IMI brain concentration was decreased. When the assessment of IMI and DMI brain level was performed 24 hr after withdrawal of IMI and CPZ or IMI and CPX, there was no difference between the concentration of IMI and DMI in both, experimental and control animals.     

Green tea polyphenols produce antidepressant-like effects in adult mice

Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like effects and the possible mechanism of action of green tea in widely used mouse models of depression. Mice were orally administered green tea polyphenols (GTP; 5, 10 and 20mg/kg) for 7days and assessed in the forced swimming test (FST) and tail suspension test (TST) 60min after the last GTP administration. Serum corticosterone and adrenocorticotrophic hormone (ACTH) levels were also determined immediately after the FST. Green tea polyphenols significantly reduced immobility in both the FST and TST but did not alter locomotor activity in the open field test, suggesting that GTP has antidepressant-like effects, and this action did not induce nonspecific motor changes in mice. Green tea polyphenols also reduced serum corticosterone and ACTH levels in mice exposed to the FST. The present study demonstrated that GTP exerts antidepressant-like effects in a mouse behavioral models of depression, and the mechanism may involve inhibition of the hypothalamic-pituitary-adrenal axis.     

Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs

Rationale  Many abused solvents share a profile of effects with classical antidepressants. For example, toluene, which is a representative and widely abused solvent, has been reported to increase both serotonin and noradrenaline levels in several brain areas after an acute exposure and to act as a noncompetitive antagonist of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptor subtype. Therefore, it is possible that toluene could possess antidepressant-like actions. Objective  To provide an initial screening of toluene’s antidepressant-like actions in the forced swimming test (FST) and the tail suspension test (TST) in mice and to analyze its possible mechanism of action. Materials and methods  Two series of experiments were performed. In the first one, male animals were exposed to toluene (0, 500, 1,000, 2,000, or 4,000 ppm) in a static exposure chamber for 30 min, and immediately after, evaluated for antidepressant-like effects. The results were compared with those obtained from mice treated with the serotonergic antidepressant clomipramine (CMI), the noradrenergic antidepressant desipramine (DMI), and the glutamatergic antidepressants, ketamine and MK-801. In the second part, we analyzed the effect of a combined administration of a subeffective concentration of toluene with a suboptimal dose of the various antidepressants acting at different neurotransmitter systems. Results  Toluene produced a concentration-dependent antidepressant-like action in the FST and TST and facilitated both MK-801 and ketamine antidepressant-like effects, but not those of DMI or CMI. Conclusions  Toluene has antidepressant-like effects that are synergized with NMDA receptor antagonists.     

Cerebral pharmacokinetics of imipramine in rats after single and multiple dosages

Summary Pharmacokinetics of imipramine (IMI) and its active metabolite, desipramine (DMI) was studied in rats after administration of a single dose of 10 mg/kg IMI, or after chronic administration of this dose once or twice a day for 14 days. The elimination curves of IMI and DMI from the blood and brain show that both the whole body and the brain behave as multi-compartment systems. Maximum concentrations of IMI and DMI in blood and brain appear at the same time, indicating rapid metabolism of IMI; the concentrations were significantly higher in the brain than in the blood. After the chronic treatment the maximum blood and cerebral levels of IMI and DMI were not much higher than after a single dose, but the elimination was slowed down. Brain concentration of IMI and DMI and brain IMI/DMI concentration ratio do not parallel those in the blood. After a prolonged treatment, once or twice a day, desipramine in the brain is present for the whole period between injections at concentrations sufficient to inhibit the noradrenaline uptake. If the drug is given twice a day, in addition to DMI also IMI is present for the whole time at concentration which may inhibit also serotonin uptake.     

Chronic dosage of imipramine in animal experiment: concentrations of imipramine and desipramine in the rat brain after various modes of dosage

Concentrations of imipramine (IMI) and desipramine (DMI) in the rat brain after administration of IMI in aqueous solution by stomach gauge twice daily, in oil solution parenterally at 48 h intervals, and with drinking water were assayed. IMI administration with the drinking water for 21 days produced a pattern of the brain concentrations of IMI and DMI similar to that observed in rats receiving IMI by stomach tube for two weeks, at 12 h intervals. When IMI was given to rats ip in an oil solution at 48 h intervals for 10 days, the brain levels of both IMI and DMI were very high and rather stable during 48 h after administration of the last dose of IMI. However, the relation between brain concentration of IMI and DMI differed markedly from that found in rats receiving IMI with the drinking water. It seems that administration of IMI with drinking water may be recommended as a reliable and convenient dosage schedule in experiments which need prolonged treatment with IMI.     

Antidepressant-like effect of icariin and its possible mechanism in mice

The behavioral, neurochemical and neuroendocrine effects of icariin isolated from Epimedium brevicornum were investigated in behavioral despair models of KunMing strain of male mice. Icariin was found to significantly shorten immobility time in the forced swimming test (FST) after orally administration for 21 consecutive days. Icarrin also produced a marked reduction in immobility time in the tail suspension test (TST) when administered for at least 7 consecutive days. The preferable antidepressant action by icariin was obtained at 17.5 and 35 mg/kg in the present study. Moreover, it was observed that the stress of FST exposure induced increases in brain monoamine oxidase (MAO) A and B activities, serum corticotropin-releasing factor (CRF) levels, as well as decreases in brain monoamine neurotransmitter levels. Treatment of icariin for 21 consecutive days mainly reversed the above effects in the mouse FST. These results suggested that icarrin possessed potent antidepressant-like properties that were mediated via neurochemical and neuroendocrine systems.     

Antidepressant-like effects of selegiline in the forced swim test.

Although selegiline, a monoamine oxidase (MAO)-B inhibitor, is reported to exert antidepressant effects in depressant patients, evidence in rodents for effects of selegiline is quite limited. The purpose of the present study was to assess effects of selegiline in the forced swim test (FST) and on locomotor activity, and to investigate whether MAO inhibition or stimulation of receptors contributes to antidepressant-like effects of selegiline. Drugs were subcutaneously administrated. The single administration of reference drug nortriptyline at 5 mg/kg reduced locomotor activity without effects in FST and brain MAO activities. But nortriptyline repeatedly given 24, 5 and 1 h before behavioral tests significantly decreased an immobility time in FST without effects in motor activities, and showed weak brain MAO-B inhibition. Single and following repeated (24, 5 and 1 h before behavioral tests) administrations of selegiline at 10 mg/kg significantly decreased the immobility time in FST, with little motor stimulant effect. In contrast, (+)-methamphetamine caused a marked decrease in immobility time and an increase in locomotor activity. Selegiline at 1 and 3 mg/kg, which failed to decrease immobility time, markedly inhibited brain total-MAO and MAO-B activities. A dopamine D1 receptor antagonist SCH 23390 completely blocked antidepressant-like effects of selegiline, but not dopamine D2, serotonergic or noradrenergic receptor antagonists. These results suggest that selegiline exerts the antidepressant-like effects by prolonging escape-directed behavior rather than by a motor stimulant effect and D1 receptor activation contributes to its effect.     

Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats

In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17beta-estradiol (E2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E2 (5, 10, 20 and 40 microg/rat) or the combination of E2 [at sub-threshold (5 microg/rat) and optimal (10 microg/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E2 at the supra-physiological doses of 10 and 20 microg/rat produced antidepressant-like effects. E2 at 5 microg/rat (that re-established the levels of this hormone to physiological levels) and at 10 microg/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST.     

Species differences in hepatic microsomal drug-metabolizing enzymes

The activity of some metabolizing enzymes was assessed in the liver microsomes of Acomys cahirinus, mice and rats. The enzymatic studies were followed by the determination of cerebral level of apomorphine (APO), imipramine (IMI) and its metabolite desipramine (DMI) of animals treated with a single dose of APO or IMI. It was found that the level of cytochrome P-450 and the activity of IMI demethylase and glucuronyltransferase in the liver microsomes of rats was significantly higher than those in the liver microsomes of Acomys and mice. The brain levels of APO, IMI and DMI were different in investigated species and IMI and DMI levels in the brain of Acomys, mice and rats corresponded to the activity of IMI demethylase in the liver microsomes of these species.