Estrogen Modulates Ethanol-Induced Memory Deficit in Postpubertal Adolescent Rats.

Abstract

Our laboratory and others have reported that ethanol (EtOH) 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, EtOH's effect on contextual fear memory was examined in postpubertal rats. In Experiment 1, intact male and female postpubertal rats were treated with an acute intraperitoneal injection of EtOH or vehicle. Thirty minutes later, rats were trained in the fear conditioning paradigm, and 24hours 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 EtOH, 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 EtOH-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 EtOH-induced contextual memory formation. Following an acute EtOH exposure, intact postpubertal female rats exhibited significant impairments in contextual fear conditioning. But acute EtOH had little effect on contextual fear conditioning in intact postpubertal males. EtOH impaired memory formation during all phases of the estrus cycle except during estrus phase when blood levels of estrogen are low. Ovariectomized rats did not show any EtOH-induced impairment in contextual freezing compared to vehicle-treated ovariectomized rats. In female rats, bilateral ovariectomy eliminated EtOH-induced memory deficit and estrogen replacement reintroduced EtOH-induced memory impairment. Although postpubertal male rats were insensitive to EtOH's effect on contextual fear conditioning, but when treated with exogenous estrogen, they performed poorly in the contextual memory task. Together, these data suggest that the female gonadal hormone estrogen is an important modulator of EtOH-induced cognitive behavior in postpubertal female and male rats, and that it may play an important role in teenage alcohol blackout.