Ethanol-Induced Loss-of-Righting Response During Ethanol Withdrawal in Male and Female Rats: Associations with Alterations in Arc Labeling
Article first published online: 6 SEP 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 2, pages 234–241, February 2012
How to Cite
Walls, S. A., Macklin, Z. L. and Devaud, L. L. (2012), Ethanol-Induced Loss-of-Righting Response During Ethanol Withdrawal in Male and Female Rats: Associations with Alterations in Arc Labeling. Alcoholism: Clinical and Experimental Research, 36: 234–241. doi: 10.1111/j.1530-0277.2011.01613.x
- Issue published online: 27 JAN 2012
- Article first published online: 6 SEP 2011
- Received for publication March 26, 2011; accepted June 4, 2011.
- Ethanol Withdrawal;
- Sex Differences;
- Loss-of-Righting Reflex
Background: There is increasing evidence for relevant sex differences in responses to ethanol. Several investigations have found differences in expression and recovery from ethanol withdrawal (EW) in people and across various animal models. We have found that female rats recover more quickly than male rats and show differential responses to various behavioral assessments and pharmacological challenges during withdrawal. The purpose of this study was to determine whether sex differences in EW behaviors extend to the hypnotic effects of acute ethanol administration.
Methods: We used a repeated measures design to assess duration and latency for loss-of-righting reflex following an acute injection of ethanol (4.2 g/kg; 20% w/v) to pair-fed control or ethanol-withdrawn animals at 1 and 3 days EW in male, female, and ovariectomized female (OVX) rats. We determined protein levels of the activity-regulated cytoskeletal protein (Arc), used as a marker for synaptic activity in glutamatergic synapses, in the motor cortex and prefrontal cortex across these same treatment conditions.
Results: Ethanol-withdrawn animals had a reduced ethanol-induced sleep time compared to controls at 1 day EW. Sleep time remained shortened at 3 days EW for males and OVX, but not females. Arc protein levels in motor cortex and preoptic nuclei significantly increased at 1 day EW across all sex conditions, suggestive of an association with the reduced ethanol-induced sleep times during EW. Arc levels increased further for males and OVX, but not females, at the 3 days EW time point.
Conclusions: These findings add further support to sex differences in effects of and responses to ethanol. They suggest that the more rapid recovery from EW for females than males also includes expression of tolerance to the hypnotic effects of ethanol. These sex differences may involve some differential neuroadaptations in glutamatergic signaling.