Chronic Intermittent Injections of High-Dose Ethanol During Adolescence Produce Metabolic, Hypnotic, and Cognitive Tolerance in Rats

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2003-10, Vol.27 (10), p.1606-1612
• Main Authors: Silvers, Janelle M., Tokunaga, Sayaka, Mittleman, Guy, Matthews, Douglas B.
• Format: Article
• Language: English
• Subjects: Adolescence; Age Factors; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Chronic Ethanol; Cognition - drug effects; Cognition - physiology; Dose-Response Relationship, Drug; Drug Tolerance - physiology; Ethanol - administration & dosage; Ethanol - blood; Hypnotics and Sedatives - administration & dosage; Male; Medical sciences; Memory - drug effects; Memory - physiology; Motor Skills - drug effects; Motor Skills - physiology; Rats; Rats, Sprague-Dawley; Spatial Memory; Tolerance; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1097/01.ALC.0000090141.66526.22

Background: Many humans are first exposed to ethanol during adolescence, the time at which they are most likely to binge drink ethanol. Chronic intermittent ethanol (CIE) exposure produces ethanol tolerance in adolescent rodents. Recent studies suggested that adolescent animals administered CIE experienced increased cognitive impairment following an ethanol challenge. These studies further explore development of ethanol tolerance caused by CIE in adolescence, and whether CIE during adolescence leads to altered ethanol response in adulthood. Methods: Beginning postnatal day (P) 30, adolescent rats were administered 5.0 g/kg ethanol or saline every 48 hours for 20 days. In experiment I, animals were tested for differential weight gain. In experiment II, loss of righting reflex (LORR) was observed after each injection, then at completion of pretreatment all animals were tested with 5.0 g/kg ethanol and LORR was observed. In experiment III, blood ethanol levels were observed and elimination rates calculated after the first and fifth pretreatments. All animals were tested with 5.0 g/kg at completion of pretreatment and elimination rates were recalculated. In experiment IV, animals were trained on the spatial version of the Morris Water Maze Task (MWMT) on non‐treatment days. Following completion of pretreatment and training, animals were tested after receiving an ethanol (1.0, 1.5, or 2.0 g/kg), or saline. Tests for experiments II, III, and IV were repeated in the same animals following 12 ethanol‐free days. Results: Chronic intermittent ethanol exposure during adolescence caused differential weight gain (experiment I). Adolescent rats developed tolerance to ethanol‐induced LORR (experiment II) and metabolic tolerance to ethanol (experiment III). This tolerance was seen after 12 ethanol‐free days. CIE also attenuated ethanol‐induced spatial memory deficits in the MWMT (experiment IV). This effect was not long‐lasting. Conclusions: Following CIE pretreatment during adolescence, tolerance developed to the hypnotic and cognitive impairing effects of ethanol, along with increased metabolic rate and decreased weight gain. These results further emphasize the ability of CIE to produce a variety of effects during adolescence, some having long‐lasting consequences.