The assessment of motor coordination is important for characterising any centrally mediated adverse effects of new chemical entities. The accelerating rotarod has previously been shown to be more sensitive to detect motor incoordination in rats compared to a fixed speed rotarod test (Bogo et al., 1981). Ethanol is known to cause motor incoordination and this effect can be exacerbated by co-administration of benzodiazepines (BNZ) (Hoffman et al., 1987). The aim of this study was to compare the sensitivity to ethanol induced motor incoordination in two acceleration speeds (0.2 and 1.0 r.p.m./s) on the rotarod with the BNZ nitrazepam as an additional comparison between the two models.

To determine the effects of ethanol and nitrazepam on motor coordination, male Sprague-Dawley rats (250-280g) were trained on the rotarod (Harvard Apparatus Coordin8®) on four separate occasions, two times per day starting two days before the test. The animals were trained to remain for either (i) 30 s on an accelerating rotarod increasing from 0 to 20 r.p.m. or (ii) for 120 s on an accelerating rotarod increasing from 4 to 12 r.p.m. On the day of testing the animals were randomised into separate groups and prior to drug administration they were tested to determine pre-dose fall time. The animals received either vehicle, nitrazepam (1 mg/kg), ethanol (2.5 mg/kg), ethanol (2.5 g/kg) + nitrazepam (0.1 mg/kg) or ethanol (2.5 g/kg) + nitrazapam (1 mg/kg). All drugs were administered p.o. with a dose volume of 10 ml/kg. The rotarod performance was assessed 60, 120 or 150 and 300 min post dose in the two speeds (accelerating 1 r.p.m./s or 0.2 r.p.m./s) and the length of time the animals were able to remain on the rotarod was recorded (fall time). The results are expressed as the mean ± SEM % of the pre-dose fall time. All data were evaluated by one-way ANOVA followed by post hoc multiple comparison Newman-Keuls tests at each time point (n=8-13).

Table 1: Effect of ethanol (2.5g/kg) (EtOH) and nitrazepam (Ntz) on rotarod performance (accelerod and accelerating).

***p<0.001 vs vehicle, **p<0.01 vs vehicle, *p<0.05 vs vehicle, ¤¤p<0.01 vs ethanol (2.5 g/kg), §p<0.05 vs ethanol (2.5 g/kg) + nitrazepam (0.1mg/kg). Nitrazepam alone and all 300 min post dose data did not significantly effect rotarod performance (p>0.05) the results are not shown.

The fast accelerating rotarod (accelerod) model is more sensitive to ethanol induced motor incoordination and the potentiating effects of nitrazapam. These results suggest that the accelerod may be a more suitable behavioural model for detecting coordination deficits in rats.

Bogo V., Hill T. A., Young R. W., et al., (1981). Neurotoxicology 2:765-787.
Hoffman PL, Tabakoff B, Szabo G, et al., (1987). Life Sci. 41:611-619.