Effects of Ethanol, MK-801, and Chlordiazepoxide on Locomotor Activity in Different Rat Lines: Dissociation of Locomotor Stimulation from Ethanol Preference

Several lines of research have suggested a link between the reward value of a drug and its ability to stimulate locomotion. One goal of the present study was to determine whether ethanol preferentially stimulates locomotor activity in lines of rat that show a preference for ethanol. A secondary goal was to determine the extent to which the benzodiazepine‐like and NMDA antagonistic action of ethanol accounted for its effect on locomotor activity. To meet these goals, the effects of varying doses of ethanol (0.125‐1.0 g/kg), MK‐801 (0.1‐0.3 mg/kg), and chlordiazepoxide (0.3‐3 mg/kg) on locomotor activity were studied in several lines of rats that had been habituated to the testing procedure. The effect of low doses of ethanol on motor activity in the Alcohol‐Preferring (P) and Fawn‐Hooded rats, which show a strong ethanol preference, were similar to those of the alcohol‐nonpreferring (NP), Flinders Sensitive Line, and Flinders Resistant Line rats. Only the Flinder Resistant Line rats showed a small, but significant increase in locomotor activity after the administration of ethanol. The highest dose of ethanol (1.0 g/kg) produced locomotor depression in all lines except the P and NP lines, which were not tested at this dose. These findings do not support a link between locomotor stimulation by ethanol and ethanol preference. In contrast, all lines exhibited locomotor stimulation after moderate (0.1‐0.3 mg/kg) doses of MK‐801, but did not exhibit increases in activity following any dose of chlordiazepoxide. These data indicate that the profiles of activity after MK‐801 and chlordiazepoxide were distinct from that of ethanol in the various rat lines. Therefore, the effects of ethanol on locomotor activity cannot be accounted for by reference solely to its antagonist‐like action at NMDA receptors and/or its agonist‐like action at GABA/benzodiazepine receptors.