Motor impairment: a new ethanol withdrawal phenotype in mice

Abstract

Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of various aspects of the complex phenotype. This study establishes motor incoordination as a new phenotype of alcohol withdrawal in mice. Mice were made physically dependent on ethanol by exposure to ethanol vapor for 72 h. The effects of ethanol withdrawal in mice from different genetic backgrounds were measured on the accelerating rotarod, a simple motor task. Ethanol withdrawal disrupted accelerating rotarod behavior in mice. The disruptive effects of withdrawal suggest a performance rather than a learning deficit. Inbred strain comparisons suggest genetic differences in magnitude of this withdrawal phenotype. The withdrawal-induced deficits were not correlated with the selection response difference in handling convulsion severity in selectively bred Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant lines. The accelerating rotarod seems to be a simple behavioral measure of ethanol withdrawal that is suitable for comparing genotypes.

Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats

“…This indicates that alcohol withdrawal did not lead to major motor impairments, but alcohol withdrawal may have caused minor performance deficits. This is in line with a previous study that reported that mice withdrawing from alcohol performed slightly less well than control mice on an accelerating rotarod test [22]. Alcohol withdrawal is associated with tremors and rigidity which may have contributed to the increase in response latencies.…”

Females uniquely vulnerable to alcohol-induced neurotoxicity show altered glucocorticoid signaling

“…BEC was determined as previously described (Beadles-Bohling and Wiren, 2006). The EtOH vapor inhalation method employed for these studies rapidly induces dependence as assessed by increased hyperexcitability, reduced exploratory behavior and increased tremor (Kosobud and Crabbe, 1986), increased motor impairment (Philibin et al, 2008), EtOH tolerance (Goldstein and Zaechelein, 1983), increased anxiety (Kliethermes et al, 2004), and increased voluntary withdrawal-induced relapse drinking (Hashimoto et al, 2011) after a single continuous 72 h period of chronic intoxication. Average BECs over the 72 h EtOH exposure period were 2.16 ± 0.09 mg/ml for EtOH exposed females and 1.98 ± 0.08 mg/ml for EtOH exposed males (unpaired t-test p > 0.05 comparing male vs. female).…”

REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?

“…A recent study reported that the motor performance of mice on a rotarod is compromised for up to 24 hr following withdrawal from chronic vapor inhalation, but is normalized by one week. These studies indicate a genetic contribution to the phenotype, since effects observed differed as a function of genetic background, and suggest that they are more likely due to compromised motor capacity than to compromised ability to acquire this task, which also involves motor learning (Philibin et al 2008). …”