Impact of adolescent alcohol use across the lifespan: Long-lasting tolerance to high-dose alcohol coupled with potentiated spatial memory impairments to moderate-dose alcohol.

Understanding how alcohol exposure during adolescence affects aging is a critical but understudied area. In the present study, male rats were exposed to either alcohol or saline during adolescence, then tested every 4 months following either an ethanol or saline challenge; animals were tested until postnatal day (PD) 532. It was found that long-lasting tolerance to high-dose ethanol exists through the test period, as measured by loss of righting reflex, while tolerance to lower doses of ethanol is not found.

Differences in Behavioral Responding in Adult and Aged Rats Following Chronic Ethanol Exposure.

Background: Research suggests symptoms of chronic alcoholism, and withdrawal may be more severe in elderly compared with younger adults. However, examination of the effects of long-term ethanol (EtOH) consumption and withdrawal is limited in aged rodents. We thus investigated EtOH withdrawal and potential deficits in cognitive and motor behavior in young adult and aged rats.

Alcohol use across the lifespan: An analysis of adolescent and aged rodents and humans.

Adolescence and old age are unique periods of the lifespan characterized by differential sensitivity to the effects of alcohol. Adolescents and the elderly appear to be more vulnerable to many of alcohol's physiological and behavioral effects compared to adults. The current review explores the differential effects of acute alcohol, predominantly in terms of motor function and cognition, in adolescent and aged humans and rodents.

Chronic intermittent ethanol exposure produces persistent anxiety in adolescent and adult rats.

Background: Ethanol (EtOH) dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors, which coincide with altered receptor subunit expression in specific brain regions. Adolescents often use EtOH at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent EtOH (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug.

The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan.

Acute alcohol produces ataxia and cognitive impairments in aged animals: a comparison between young adult and aged rats.

Background: Aging in both humans and rodents appears to be accompanied by physiological changes that increase biologic sensitivity to ethanol (EtOH) intoxication. However, animal models designed to investigate this increased alcohol sensitivity have yet to be established. For this reason, we sought to determine whether acute EtOH administration produces differential effects on motor coordination and spatial cognition in young adult and aged rats.

The effect of chronic intermittent ethanol exposure on spatial memory in adolescent rats: the dissociation of metabolic and cognitive tolerances.

Using a rapid chronic intermittent ethanol (CIE) vapor exposure paradigm, we demonstrate the dissociability of metabolic tolerance from cognitive tolerance in adolescent rats. Adolescent rats were trained to spatially navigate in the Morris Water Maze and then exposed to CIE vapor or air 16 h a day for 4 days. After a final 28 h withdrawal, all rats received a saline or ethanol challenge, followed by a test of spatial memory 30 min after administration.

Low and moderate doses of acute ethanol do not impair spatial cognition but facilitate accelerating rotarod performance in adolescent and adult rats.

Adolescents and adult rodents have differing sensitivities to the acute effects of ethanol on a variety of behavioral and electrophysiological measures. Often, these differences are revealed using high ethanol doses and consequently little is known about these age-related effects using lower ethanol doses. We sought to determine if low-dose ethanol produces differential effects on cognition and motor behavior in adolescent and adult rats.

Behavioral effects of ethanol in cerebellum are age dependent: potential system and molecular mechanisms.

Background: Adolescent rats are less sensitive to the motor-impairing effects of ethanol than adults. However, the cellular and molecular mechanisms underlying this age-dependent effect of ethanol have yet to be fully elucidated.

Method: Male rats of various ages were used to investigate ethanol-induced ataxia and its underlying cellular correlates.

The influence of a chronic adolescent nicotine exposure on ethanol withdrawal severity during adulthood in C3H mice.

Animal and human studies have shown tolerance, consumption, relapse, and behavioral interactions between ethanol and nicotine, but little is understood about their interaction, especially as it relates to ethanol withdrawal in adulthood for subjects who have an adolescent history of using these drugs. This study investigated nicotine's influence on ethanol withdrawal seizures in two different age groups of male C3H mice. Adolescent and adult male C3H mice, beginning at postnatal day 28 or 70, respectively, were subjected to a 7-day chronic exposure to ethanol only, ethanol plus nicotine, nicotine only, or vehicle treatment.

The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress.

The past decade has brought many advances in our understanding of GABA(A) receptor-mediated ethanol action in the central nervous system. We now know that specific GABA(A) receptor subtypes are sensitive to ethanol at doses attained during social drinking while other subtypes respond to ethanol at doses attained by severe intoxication. Furthermore, ethanol increases GABAergic neurotransmission through indirect effects, including the elevation of endogenous GABAergic neuroactive steroids, presynaptic release of GABA, and dephosphorylation of GABA(A) receptors promoting increases in GABA sensitivity.

Investigation of ethanol-induced impairment of spatial memory in gamma2 heterozygous knockout mice.

GABA(A) receptors, the major inhibitory receptors in the mammalian central nervous system, are affected by a number of drug compounds, including ethanol. The pharmacological effects of certain drugs have been shown to be dependent upon specific GABA(A) receptor subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the gamma2-containing GABA(A) receptors as a mechanism of action.

Chronic intermittent exposure to ethanol during adolescence produces tolerance to the hypnotic effects of ethanol in male rats: a dose-dependent analysis.

Adolescence is a time period when distinct behavioral and neurophysiological changes occur. Novelty seeking is common during this developmental period, and binge alcohol consumption by adolescents is prevalent. Adolescents, as compared to adults, have been shown to display decreased sensitivity to many effects of ethanol, including effects that may serve as cues to moderate consumption.

The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.

Background: Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol.

Periadolescent exposure to ethanol and diazepam alters the aversive properties of ethanol in adult mice.

Evidence suggests that the developing adolescent brain may be especially vulnerable to long-term neurobehavioral consequences following ethanol exposure and withdrawal. In the present study, we examined the long-term effect of adolescent ethanol withdrawal on a subsequent EtOH-induced conditioned taste aversion (CTA). Periadolescent and adult C3H mice were exposed to 64 h of continuous (single withdrawal) or intermittent (multiple withdrawal) ethanol vapor.