Estrogen Modulates Ethanol‐Induced Memory Deficit in Postpubertal Adolescent Rats

Abstract

Background Our laboratory and others have reported that ethanol impairs hippocampus‐associated memory formation in prepubertal adolescent rats. Acute alcohol exposure in humans produces a syndrome of memory loss (“blackouts”) that is similar to impairments caused by hippocampal damage. The ability to form new long–term explicit memories is affected but not short–term memory storage or recall of information from long–term storage. Alcohol‐induced memory impairment, similar to teenage alcohol blackouts, has been shown in prepubertal adolescent rodents. In the present study, ethanol's effect on contextual fear memory was examined in postpubertal rats. Methods In Experiment 1, intact male and female postpubertal rats were treated with an acute intraperitoneal injection of ethanol or vehicle. Thirty minutes later, rats were trained in the fear conditioning paradigm, and 24h after training all rats were tested for contextual fear conditioning. In Experiment 2, groups of intact postpubertal female rats were treated with a single injection of ethanol, or vehicle, during different phases of the estrus cycle, and tested for fear conditioning. In Experiment 3, groups of postpubertal female rats were ovariectomized (OVX) and were given hormonal supplementation (estrogen with or without progesterone) and tested for ethanol‐induced memory formation. Additional controls included sham‐operated, oil‐treated postpubertal female rats. In Experiment 4, intact postpubertal male rats were administered exogenous estrogen alone or together with progesterone, and tested for ethanol‐induced contextual memory formation. Results Following an acute ethanol exposure, intact postpubertal female rats exhibited significant impairments in contextual fear conditioning. But acute ethanol had little effect on contextual fear conditioning in intact postpubertal males. Ethanol impaired memory formation during all phases of the estrus cycle except during estrus phase when blood levels of estrogen are low. OVX rats did not show any ethanol‐induced impairment in contextual freezing compared to vehicle‐treated OVX rats. In female rats bilateral ovariectomy eliminated ethanol‐induced memory deficit and estrogen replacement reintroduced ethanol‐induced memory impairment. Although postpubertal male rats were insensitive to ethanol's effect on contextual fear conditioning when treated with exogenous estrogen, they performed poorly in the contextual memory task. Conclusion Together, these data suggest that the female gonadal hormone estrogen is an important modulator of ethanol‐induced cognitive behavior in postpubertal female and male rats, and that it may play an important role in teenage alcohol blackout.