Chronic intermittent ethanol exposure during adolescence blocks ethanol-induced inhibition of spontaneously active hippocampal pyramidal neurons.
BACKGROUND
Binge alcohol drinking among adolescents has been a serious public health problem. A model of binge alcohol, chronic intermittent ethanol exposure (CIEE), during adolescence significantly attenuates ethanol-induced spatial memory deficits in rats. However, the attenuation was absent following a 12-day ethanol-free period. Since spatial memory is hippocampal dependent, a reduction in ethanol-induced spatial memory impairments may be due to a reduction in the ability of ethanol to inhibit the firing rate of single hippocampal pyramidal neurons following CIEE.


METHODS
Beginning on postnatal day 30 (P30), male adolescent Sprague-Dawley rats (Harlan) were administered 5.0 g/kg ethanol (n = 10, CIEE-treated group) or an equivolume saline (n = 10, CISE-treated group) every 48 hours for 20 days. Single hippocampal pyramidal neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded on the day following completion of the chronic intermittent exposure procedure (animals now P50). Additionally, neurons from 5 CIEE-treated rats and 5 CISE-treated rats were recorded 12 days after the completion of the chronic intermittent exposure procedure (animals now P62).


RESULTS
Ethanol exposure during adolescence completely blocked ethanol-induced inhibition of hippocampal pyramidal neurons in rats that were CIEE exposed. However, the effect of CIEE on hippocampal neurophysiology was time dependent. Specifically, neurons recorded from CIEE-treated rats after a 12-day ethanol-free period had similar maximal inhibition as neurons from CISE-treated animals, although the time to reach inhibition was significantly greater in neurons from CIEE-treated rats.


CONCLUSIONS
Chronic ethanol exposure during adolescence produces a reduction, or tolerance, to ethanol-induced inhibition of hippocampal pyramidal neural activity. Although the tolerance was greatly reversed after a 12-day ethanol-free period, neurons from CIEE animals inhibited slower than neurons from CISE animals. Since the hippocampus is known to be involved not only in spatial memory, but also in many other types of memory formation, the altered hippocampal functions because of CIEE during adolescence should be taken as a serious warning for society.
Tokunaga
Sayaka
S
Department of Pharmacology, University of Tennessee, Memphis, Tennessee, USA.
Silvers
Janelle M
JM
Matthews
Douglas B
DB
D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004361:Drug Tolerance; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol