Estrogen Modulates Ethanol‐Induced Memory Deficit in Postpubertal Adolescent Rats

Abstract

Background: Our laboratory and others have reported that ethanol (EtOH) impairs hippocampusassociated 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.Methods: 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 24 hours 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.Results: 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.Conclusions: 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.

Behavioral changes and dendritic remodeling of hippocampal neurons in adolescent alcohol-treated rats

“…Another hippocampus related behavior modulated by alcohol in adolescent rats is contextual fear conditioning. Acute administration of alcohol in adolescent rats has been reported to impair contextual fear conditioning [ 10 ]. When tested as adults, repeated alcohol exposure in adolescent rats caused deficits in context fear conditioning but not in cued fear memory [ 11 ].…”

“…When tested as adults, repeated alcohol exposure in adolescent rats caused deficits in context fear conditioning but not in cued fear memory [ 11 ]. Gender differences have been reported in alcohol-induced memory functions both in humans and animals, with females being more susceptible to alcohol’s amnesic effects than males [ 10 , 12 – 14 ].…”

Sex differences in the acute ethanol effects on object recognition memory: influence of estrous cycle

“…The effects of acute ethanol (EtOH) on learning and memory have been investigated in human and rodent students, and memory deficits are usually reported (Lister et al , 1987; Silvers et al , 2003; Matthews and Silvers, 2004; Zorumski et al , 2014; Miyake et al , 2020). Nevertheless, these effects are dependent on several factors such as behavioral task, dose, acquisition/retrieval interval, age, sex, and estrogen levels (Matthews et al, 1995; 1999; Kameda et al , 2007; Broadwater and Spear, 2013; Boissoneault et al , 2014; Hoffman et al , 2015; Hunt and Barnet, 2016; Lewis et al , 2019; Sircar, 2019).…”

Sex difference in the vulnerability to hippocampus plasticity impairment after binge‐like ethanol exposure in adolescent rat: Is estrogen the key?

“…Memory loss, called “blackout,” a kind of temporary anterograde amnesia 16 is frequently experienced by teenagers, 16 and one predictive factor of “blackout” experiences is female sex, 16 which is in accordance with a higher vulnerability of female to ethanol‐induced cognitive impairment 9,12 . Preclinical studies described ethanol‐induced memory impairments in males or females, 17–20 with a possible role of estrogen in female 21,22 . However, there is a lack of demonstration that higher vulnerability to memory impairments in female rodents includes a role for circulating estrogen.…”

“…9,12 Preclinical studies described ethanol-induced memory impairments in males or females, [17][18][19][20] with a possible role of estrogen in female. 21,22 However, there is a lack of demonstration that higher vulnerability to memory impairments in female rodents includes a role for circulating estrogen. Estrogen is acknowledged as a promnesiant hormone facilitating long-term synaptic potentiation (LTP) in rodent hippocampus and increasing learning.…”