This research was supported by the National Institute on Alcohol Abuse and Alcoholism Grant R01 AA10288.
Decreased Sensitivity to the Hypnotic Effects of Ethanol Early in Ontogeny
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 3, pages 670–676, May 1998
How to Cite
Silveri, M. M. and Spear, L. P. (1998), Decreased Sensitivity to the Hypnotic Effects of Ethanol Early in Ontogeny. Alcoholism: Clinical and Experimental Research, 22: 670–676. doi: 10.1111/j.1530-0277.1998.tb04310.x
We would like to thank Tamara R. Allen for her excellent technical assistance in the conduct of this project and Dr. Celia Klin for her invaluable statistical expertise.
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication May 8, 1997; accepted December 8, 1997
- Key Words: Ontogeny;
- Sleep Time;
- Acute Tolerance;
- Waking Alcohol Levels
Sensitivity to the hypnotic effects of ethanol was examined in Sprague-Dawley male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep times were recorded and blood alcohol levels (BALs) and brain alcohol levels (BrALs) were measured upon awakening. In addition to examining ethanol sleep time during ontogeny, data were used to estimate acute tolerance (indexed by the slope of the linear regressions of waking BALs and BrALs as a function of dose) and initial brain sensitivity to ethanol (indexed by calculating the y-intercept from the linear regression of BrALs as a function of sleep time). The results showed a marked increase in sensitivity to ethanol hypnosis during ontogeny, with young animals exhibiting shorter ethanol-induced sleep times and high waking BALs and BrALs. This ontogenetic increase in ethanol sensitivity was associated with a developmental decline in acute tolerance, with acute tolerance being most pronounced at postnatal day (P) 16 and evident only up to P36. Initial sensitivity conversely increased with age, with P16 pups showing lower initial brain sensitivity to ethanol than at all other ages. Gender differences emerged in adulthood, with males sleeping significantly longer than females at P56 and P96. These findings suggest that the marked insensitivity of young animals to the hypnotic effects of ethanol is related to both pronounced acute tolerance, as well as reduced initial brain sensitivity to ethanol early in life.