The Effects of Traditional Tonics on Fatigue in Mice Differ from Those of the Antidepressant Imipramine: A Pharmacological and Behavioral Study

American Journal of Chinese Medicine, Wntr, 2000 by Takeshi Tadano, Osamu Nakagawasai, Fukie Niijima, Koichi Tan-No, Kensuke Kisara

Results

Effects of NTD and Imipramine on Locomotor Activity and Forced Swimming

After pretreatment with tetrabenazine (100 mg/kg, i.p.), each sample (S-1, 973%; S-2, 1069%; S-3, 1154%) and imipramine (5 mg/kg, 213%; 10 mg/kg, 384%; 20 mg/kg, 565%) showed an increase in the locomotor activity. The effect of imipramine, however, was significantly less than that induced by each tonic drug. After preloading by forced swimming for 5 min, all of the tonics (S-1, 25%; S-2, 18%; S-3, 6%) significantly reduced the duration time of immobility, compared to the non-preloaded mice (S-1, 81%; S-2, 75%; S-3, 69%) (Tables 1 and 3). In addition, without the preloading of forced swimming or the pretreatment with tetrabenazine, the efficacy of each sample (S-1, 226%; S-2, 246%; S-3, 260%) on locomotor activity was weak, compared to mice who had preloading. Tetrabenazine (100 mg/kg, i.p.) given to mice 24 hr before treatment with water also caused a significant increase in the duration of immobility as compared to those not given tetrabenazine. The increased duration time of immobility induced by the administration of tetrabenazine was reduce significantly by each tonic (S-1, 45%; S-2, 36%; S-3, 2%). In contrast, after preloading by forced swimming for 5 min, imipramine did not show any change in the duration time of immobility (5 mg/kg, 117%; 10 mg/kg, 114%; 20 mg/kg, 99%), but that was not the case in the mice who received pretreatment with tetrabenazine (Table 3).

Table 3. Effects of S-1, -2, -3 and Imipramine (IMP) after Pretreatment with Tetrabenazine (TBZ) or Preloading Forced Swimming on Locomotor Activity and the Duration of Immobility

Locomotor Activity (% of Control)

                    Imipramine (mg/kg)         Sample

                     5      10     20     1       2       3

Non-pretreatment    105%   113%   111%   226%    246%    260%
Pretreatment with   213%   384%   565%   973%   1069%   1154%
TBZ (100 mg/kg)

Duration of Immobility (% of Control)

                    Imipramine (mg/kg)          Sample

                     5      10     20     1       2       3

Swimming Load       117%   114%   99%    25%     18%      6%
Pretreatment with    69%    50%   33%    45%     36%     21%
TBZ (100 mg/kg)

The duration of immobility was measured 1 hr after injection of S-1, S-2, S-3 or IMP. S (1-3) and IMP was given 24 hr after the injection of tetrabenazine (TBZ).

Effects of NTD (S-3) and Imipramine on the Swimming Pattern Induced by Forced Swimming

As shown in Table 3, after preloading stress the effect of S-3 was different from that induced by imipramine. To clarify this difference between NTD and imipramine, the duration time of immobility, struggle and swimming after pretreatment with tetrabenazine (200 mg/kg, i.p.) were observed for 15 min using forced swimming. During the first 0~5 min after the tetrabenazine injection, the duration time of each swimming pattern did not show a significant change as compared to that induced by imipramine. At 5~10 min and 10~15 min after the tetrabenazine injections, the duration time of swimming (6~10 sec) and straggle (0~5 sec) were short with imipramine (swimming, 5~10 min: 26 sec; 10~15 min, 5 sec). In contrast, S-3 showed a prolonged effect on the duration of swimming at 5~10 min (99 sec) and 10~15 min (73 sec) after the tetrabenazine injection (Figure 1).