Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol

Abstract

Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety.

Introduction

Ethyl alcohol (alcohol) intake can result in major behavioral disturbances, including disruption of motor functions. In rats, alcohol can alter locomotor activity, coordination [3], [4], [7], [13], [23], [34], [58], and movement initiation [33], [56]. Alcohol consumption in humans similarly affects locomotion and high doses have been shown to induce tremor, rigidity, and difficulty in fine hand movements and body posture [10], [44]. In addition to its effects on movement, alcohol has addictive properties [8], [18], [28], [59]. In vivo and in vitro studies showing that alcohol stimulates dopaminergic neurons [8], and alters dopamine (DA) and enkephalin turnover [5], [9], [15], [24], [30], [31], [45], [54], [65], [66], suggest that its addictive properties might be mediated by these neurotransmitters. Furthermore, alcohol can affect motor system function via interactions with various other neurotransmitter systems, such as glutamate [12], [29], [60], GABA (e.g. [7], [21], [26]) and serotonin (e.g. [20], [25]). Alcohol also has been shown to antagonize stress-induced activation of the prefrontal dopaminergic system [22], [32], an action that might underlie its anxiolytic actions [11], [51].

In most tests of the effects of alcohol on behavior in rats, only tests of gross locomotion or coordination have been used. This raises the question of whether alcohol might similarly impair skilled limb movements. There is evidence to suggest that skilled movements may require the use of different neural systems than those used for whole body movements. For example, damage to the pyramidal tract severely impairs skilled reaching for food in the rat [63], [67], but walking on a smooth surface is not affected [37], [42]. In addition, studies in which motor subsystems have been examined indicated that the neural mechanisms underlying postural support and its allied reflexes are at least partially different from the neural mechanisms underlying locomotion and its allied reflexes [16], [17], [56]. For instance, animals that have received injections of the major tranquilizer haloperidol or which have received DA depletions using the neurotoxin 6-hydroxydopamine (6-OHDA), have preserved postural support and defend postural support with reflexes of bracing, even though they are relatively unable to locomote [47], [55]. On the other hand, animals treated with morphine, minor tranquilizers, or amphetamine lose postural support but will step and walk [16], [17]. Although there has been analysis of the effects of alcohol on posture and locomotion, there has been no examination of the effects of alcohol on skilled movements in rats. On the basis of previous studies on motor behavior of rats under the effects of alcohol, it might be expected that alcohol would disrupt both the accuracy and the movements that rats use to reach for food. On the other hand, given that movement subsystems underlying skilled movement and whole body movements are at least partly independent, it is possible that alcohol might have differential effects on skilled movement and whole body movements.

We had an additional interest in examining the effects of alcohol on skilled movements. Animals that perform poorly often rush and become frantic in their attempts to obtain food. Given the evidence that alcohol can have anxiolytic effects, it seemed possible that alcohol might improve reaching success by reducing frustration and anxiety. Given that alcohol can stimulate release of DA [66], which might mediate its rewarding and anxiolytic actions, we included a group of rats that had received unilateral DA-depletions. Rats with such unilateral lesions typically are impaired in skilled reaching with their contralateral-to-lesion forelimb but do achieve some successes [36], [38]. The prediction was that changes produced by alcohol on skilled reaching might be mediated by DA.