Ethanol induces locomotor activating effects in preweanling Sprague-Dawley rats

Abuse of drugs exerts biphasic motor activity effects, which seem to be associated with their motivational effects. In the case of ethanol, heterogenous rat strains appear to be particularly sensitive to the sedative effects of the drug. In contrast, ethanol's activating effects have been consistently reported in rats genetically selected for ethanol affinity. Heightened ethanol affinity and sensitivity to ethanol's reinforcement are also observed in nonselected rats during early ontogeny. In the present study, we examined psychomotor effects of ethanol (1.25 and 2.5 g/kg) in 8-, 12-, and 15-day-old pups. Motor activity in a novel environment was assessed 5-10 or 15-20 min following drug treatment. Rectal temperatures and latency to exhibit the righting reflex were recorded immediately after locomotor activity assessment. Ethanol exerted clear activating effects at 8 and 12 days of age (Experiments 1a and 1b) and to a lesser extent at 15 days. At this age, ethanol enhanced locomotor activity in the first testing interval (Experiment 1b) and suppressed locomotion at 15-20 min (Experiment 1a). Ethanol-mediated motor impairment was more pronounced in the youngest group (postnatal day 8) than in the older ones. Blood ethanol concentrations were equivalent in all age groups. The present study indicates that preweanling rats are sensitive to ethanol's stimulating effects during the second postnatal week, and suggest that specific periods during early ontogeny of the rat can provide a valuable framework for the study of mechanisms underlying ethanol's stimulation and reinforcement effects.     

Ethanol-induced stimulation and depression on measures of locomotor activity: Effects of basal activity levels in rats

Male Sprague-Dawley rats selected for low (LA) and high activity (HA) were used to investigate the biphasic actions of ethanol (EtOH) (20% v/v) on spontaneous measures of activity. Following IP injections of low to moderate doses of EtOH (0.10 g/kg and 0.50 g/kg), horizontal and vertical activities were assessed at 0–10- and 30–40-min intervals. Rats preselected for LA exhibited an increase in performance on both measures. The stimulatory effect, however, was observed only during the 0–10-min session with the lowest dose of EtOH (0.10 g/kg). The 0.50-g/kg dose had no effect on either measure at the 0–10-min interval; however, both doses suppressed activity at the 30–40-min interval. In contrast, activity was suppressed in HA animals independent of the EtOH dose level or time interval. These results demonstrate that basal response profiles are important predictors of behavioral activation following low stimulant doses of EtOH. Moreover, the results demonstrate the importance of selecting animals for basal activity levels to reliably interpret the mechanisms controlling the stimulant and depressant effects of EtOH.     

Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake

To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity.     

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood.     

Sensitization to social anxiolytic effects of ethanol in adolescent and adult Sprague-Dawley rats after repeated ethanol exposure

Ontogenetic studies using a social interaction paradigm have shown that adolescent rats are less sensitive to anxiolytic properties of acute ethanol than their adult counterparts. It is not known, however, whether adaptations to these anxiolytic effects on repeated experiences with ethanol would be similar in adolescents and adults. The present study investigated sensitivity to the anxiolytic effects of ethanol in adolescent and adult male and female Sprague-Dawley rats after 7 days of exposure (postnatal day [P] 27-33 for adolescents and P62-68 for adults) to 1 g/kg ethanol or saline (intraperitoneally]) and in animals left nonmanipulated during this time. Anxiolytic effects of ethanol (0, 0.75, 1.0, 1.25, and 1.5 g/kg for adolescents and 0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg for adults in experiments 1 and 2, respectively) were examined 48 h after the last exposure using a modified social interaction test under unfamiliar test circumstances. At both ages, repeated ethanol exposure resulted in the development of apparent sensitization to anxiolytic effects of ethanol, indexed by enhancement of social investigation and transformation of social avoidance into social indifference or preference and expression of tolerance to the socially inhibiting effects induced by higher ethanol doses. Evidence for the emergence of sensitization in adults and tolerance at both ages was seen not only after chronic ethanol but also after chronic saline exposure, suggesting that chronic manipulation per se may be sufficient to alter the sensitivity of both adolescents and adults to socially relevant effects of ethanol.     

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. Consequently, reduction of these factors could facilitate drinking behaviors in adolescents, which may disrupt normal developmental processes. Chronic intermittent ethanol exposure (CIEE) to high doses of ethanol in rats has been shown to prevent normal developmental increases in sensitivity to ethanol-induced loss of righting reflex (LORR). However, it is unknown whether the same disruptions would occur following CIEE to more moderate and low alcohol doses. The present study was designed to evaluate the effects of CIEE in rats to several different doses during adolescence on ethanol-induced LORR in adulthood. Male rats were weighed and treated intraperitoneal with 1.0, 2.0, 3.0, or 4.0 g/kg ethanol or equivolume saline (equivalent to 4.0 g/kg dosings) every 48 hours for 20 days beginning on postnatal day (PN) 30. LORR was measured following each ethanol exposure. Finally, LORR was measured in both ethanol and saline-exposed animals following 4.0 g/kg ethanol challenge on PN 50 and following a 12-day withdrawal period (PN62). Duration of LORR remained unchanged throughout the adolescent exposure period. However, when LORR was measured on PN50 and PN62, 4.0 and 3.0 g/kg treatment groups displayed significantly less LORR compared to the free feeding and 1.0 g/kg ethanol treated groups. Animals displayed no tolerance development to LORR throughout the chronic exposure period even though moderate and high doses of ethanol were used. CIEE to high (3.0 or 4.0 g/kg) doses of ethanol disrupted the expected developmental increase in sensitivity to ethanol-induced LORR. These results may have implications for human adolescent drinkers. Specifically due to adolescents' relative resistance to the hypnotic effects of alcohol and their tendency to intake alcohol in an intermittent, or binge-like, manner such tolerance might lead to increases in alcohol abuse in this population of drinkers.     

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17–20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development.     

Activity and social behavior in a complex environment in rats neonatally exposed to alcohol

Environmental complexity (EC) is a powerful, stimulating paradigm that engages animals through a variety of sensory and motor pathways. Exposure to EC (30 days) following 12 days of wheel running preserves hippocampal neuroplasticity in male rats neonatally exposed to alcohol during the third-trimester equivalent (binge-like exposure on postnatal days [PD] 4–9). The current experiment investigates the importance of various components of EC (physical activity, exploration, social interaction, novelty) and examines whether neonatal alcohol exposure affects how male rats interact with their environment and other male rats. Male pups were assigned to 1 of 3 neonatal conditions from PD 4–9: suckle control (SC), sham-intubated (SI), or alcohol-exposed (AE, 5.25 g/kg/day). From PD 30–42 animals were housed with 24-h access to a voluntary running wheel. The animals were then placed in EC from PD 42–72 (9 animals/cage, counterbalanced by neonatal condition). During EC, the animals were filmed for five 30-min sessions (PD 42, 48, 56, 64, 68). For the first experiment, the videos were coded for distance traveled in the cage, overall locomotor activity, time spent near other animals, and interaction with toys. For the second experiment, the videos were analyzed for wrestling, mounting, boxing, grooming, sniffing, and crawling over/under. AE animals were found to be less active and exploratory and engaged in fewer mounting behaviors compared to control animals. Results suggest that after exposure to wheel running, AE animals still have deficits in activity and social behaviors while housed in EC compared to control animals with the same experience.     

The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol

Mice were made tolerant to the hypothermic effect of ethanol by repeated administration of ethanol (4 g/kg, 25% v/v, IP) on three consecutive days. The colonic temperature was measured in individually-housed animals immediately before and 45 min after ethanol treatment. Peptide treatments with various schedules were made SC 2 hr before the first ethanol challenge. The decrease in hypothermic response was accepted as a tolerance phenomenon, which developed in control animals by day 2. A single injection of oxytocin (OXT) or lysine vasopressin (LVP [0.1 or 1 IU peptide] animal) before the first ethanol injection did not change the initial sensitivity to ethanol. This absence of acute interactions is also reflected in the sleep onset and sleep duration after 5 g/kg ethanol (IP). In contrast, both OXT and LVP affected the development of tolerance. Repeated treatments with graded doses of OXT (0.5-2 IU) or LVP (0.25-1 IU) every day for 3 days blocked the development of tolerance. 0.002 IU LVP facilitated the development of hypothermic tolerance. The remaining doses of the peptides were ineffective. A high dose of LVP (1 IU) facilitated hypothermic tolerance if the peptide was injected when tolerance to ethanol had developed fully without previous peptide treatment. OXT, on the other hand, was ineffective in this particular experimental model. The data suggest that both neurohypophyseal hormones (LVP and OXT) block the early developmental phase of tolerance to ethanol. On the other hand, LVP facilitated the expression of tolerance if the peptide was given to mice with fully developed tolerance.     

The inhibitory effect of testosterone on the development of metabolic tolerance to ethanol

We have investigated the mechanism(s) of metabolic tolerance to ethanol in a rat strain (spontaneously hypertensive or SH) in which liver alcohol dehydrogenase (ADH) levels are very low due to a marked inhibitory effect of testosterone on ADH. Chronic ethanol administration resulted in marked increases in the rate of ethanol metabolism and in ADH activity (+65 to 90%). Oxygen consumption measured in the perfused livers of the ethanol-fed rats was also elevated (+40%). The administration of 6-n-propyl-2-thiouracil (PTU), which was previously found to reduce hepatic oxygen consumption and to increase ADH activity, resulted in no change in the rate of ethanol metabolism in the ethanol-fed rats and an increase in the sucrose-fed controls, suggesting that increased ADH activity is more important for the development of metabolic tolerance to ethanol, in the male SH rat, than increased oxygen consumption. The activity of the microsomal ethanol-oxidizing system (MEOS) in vitro was induced by chronic ethanol treatment (+95%), but it may only account for a small part (32%) of the increase in ethanol metabolism in vivo. Serum testosterone concentrations were lower in the ethanol-fed rats at peak blood ethanol levels, relative to those found in controls. Concurrent chronic administration of ethanol and testosterone abolished about one-third of the absolute increases in ethanol metabolism and in ADH activity in the ethanol-fed rats. In conclusion, most of the metabolic tolerance to ethanol, in the male SH rat, appears to occur mainly due to a testosterone-independent increase in ADH activity and to a lesser degree to an increase in ADH activity produced by a reduction in testosterone levels in the ethanol-fed rats.     

Differential motivational properties of ethanol during early ontogeny as a function of dose and postadministration time.

While appetitive reinforcement effects of ethanol are easily detected in rat neonates, such phenomena rarely have been observed in older infants. Recently, Molina et al. [Molina, J. C., Ponce L. F., Truxell, E., & Spear N. E. (2006). Infantile sensitivity to ethanol's motivational effects: ethanol reinforcement during the third postnatal week. Alcohol Clin Exp Res 30, 1506-1519] reported such effects of ethanol in 14-day-olds using a second-order conditioning procedure. Infants also appear to be sensitive to biphasic reinforcement or general motivational effects of ethanol, with appetitive effects seeming to occur early in the state of intoxication and aversive effects predominant during late stages, but tests have been inconclusive. The present study examined the possibility of biphasic motivational effects of ethanol during infancy through the use of second-order conditioning procedures. Preweanling rats (14 days old) experienced intraoral water infusions (conditioned stimulus, CS) either 5-20 or 30-45 min after administration of 0.5 or 2.0 g/kg i.g. ethanol. Pups were then exposed to the CS while over a novel texture (second-order phase). Tests of tactile preference for that texture followed. Locomotive, thermal, hormonal (corticosterone release), and pharmacokinetic patterns likely to underlie the acquisition of ethanol-mediated conditioning were also examined in subsequent experiments. Intraoral CSs paired with either early or late effects of low-dose ethanol (0.5 g/kg, blood ethanol concentration: 40 mg%) became positive second-order reinforcers. Appetitive effects were also exhibited by pups exposed to the CS during commencement of the toxic episode induced by a 2.0 g/kg ethanol dose, 5-20 min after administration of ethanol, whereas aversions emerged when CS presentation occurred 30-45 min postadministration time (blood ethanol concentrations: 157 and 200 mg%, respectively). Overall, the results indicate that infants rapidly detect differential motivational properties of ethanol as a function of dose or drug postadministration time. Relatively neutral stimuli associated with these properties are later capable of acting as either positive or aversive reinforcers. Thermal and motor responses that accompany ethanol intoxication do not seem to be directly associated with differential hedonic properties of the drug at this stage of development.     

铅和乙醇对雄性大鼠生殖系统的联合毒作用

采用整体动物实验方法,观察铅和乙醇对大鼠精子数量和质量,以及血中性激素水平的联合作用。结果显示,精子计数联合组比铅和乙醇单独作用组显著减少;精子活动度分析联合组与其他各组比较显著下降。铅和乙醇单独作用均可使雄性大鼠血清睾酮(T)升高,促黄体生成激素(LH)下降,联合作用使T降低,LH较单独作用组升高。提示铅和乙醇联合染毒对雄性大鼠生殖毒性影响可能具有增毒作用。     

Alcohol self-administration in rats: Modulation by temporal parameters related to repeated mild social defeat stress

Clinical evidence often points to stress as a cause or an antecedent to the development of drinking problems. Yet, animal models of alcohol drinking have yielded inconsistent evidence for a direct contribution of stress, and many studies have shown that stress suppresses alcohol consumption. The aim of the present study was to examine alcohol reward in animals exposed to repeated, mild social stress, and to determine whether alcohol drinking changes as a function of the temporal parameters of alcohol access relative to the stressor. Male Long-Evans rats, trained to self-administer a 6% (wt/vol) alcohol solution using a sucrose-fading procedure, were exposed to five brief (5 min) episodes of contact with an aggressive male. Full contact with the resident was limited to a single episode of defeat, whereas the following four encounters occurred with the subjects behind a protective wire mesh cage. Alcohol self-administration was measured 1 week prior to stress (baseline), on each day of stress exposure, and 1 week following stress. Separate groups of animals were randomly assigned to self-administer alcohol immediately prior, immediately following, or 2 h following defeat stress. Stress preferentially increased alcohol drinking on stress-exposure days, and further elevated the amount consumed 1 week following stress. Temporal parameters of alcohol access relative to the stressor were found to be important. Average alcohol consumption was greatest for animals drinking 2 h postdefeat, whereas animals drinking immediately prior to or following the stressor did not show a significant increase in alcohol consumption. Results suggest that mild social defeat stress is sufficient to elicit increases in alcohol consumption in nonpreferring strains of rodents, provided alcohol access occurs at an optimal time interval after the social defeat experience.     

Differential patterns of expression of neuropeptide Y throughout abstinence in outbred Swiss mice classified as susceptible or resistant to ethanol-induced locomotor sensitization

Several studies have focused on the negative emotional state associated with drug abstinence. The peptide NPY plays an important role given its involvement in drug addiction, anxiety, and mood disorders. Interestingly, it is well established that outbred Swiss mice exhibit a prominent behavioral variability to ethanol-induced locomotor sensitization. Here, we investigated whether mice that were either susceptible or resistant to ethanol sensitization differed in their NPY expression during abstinence. The mice were treated daily with ethanol (2 g/kg, i.p.) or saline for 21 days. According to the locomotor activity after the last injection, the ethanol group was classified as sensitized (EtOH_High) or non-sensitized (EtOH_Low). To evaluate NPY expression, some of the mice were sacrificed at 18 h or 5 days of abstinence, and others were challenged at the 5th day of abstinence with ethanol (1.4 g/kg) and sacrificed after 1.5 h. At 5 days of abstinence, NPY expression increased in the orbital cortex, dorsomedial striatum, and dentate gyrus in the EtOH_High mice. These changes were counteracted by the ethanol challenge. In the EtOH_Low mice, NPY expression increased in the dentate gyrus only after 18 h of abstinence. Lastly, a decreased level of NPY was found in the prelimbic cortex of the EtOH_Low mice at 5 days of abstinence, and this was reversed by ethanol challenge. Therefore, behavioral variability in ethanol sensitization confers differential neurochemical features during the subsequent abstinence, including distinct patterns of NPY expression.     

Differential effects of ethanol and midazolam upon the devaluation of an aversive memory in infant rats.

In infant rats, low doses of ethanol (EtOH) have been found to attenuate the aversive representation of an unconditioned stimulus (US) as assessed through a revaluation paradigm. This may be explained by early anxiolytic properties of EtOH. The present set of experiments was aimed at analyzing possible mechanisms of these putative antianxiety effects of EtOH. In the first experiment, EtOH's effects upon the expression of citric acid-induced distress calls were compared with varying doses of midazolam (MDZ), a fast-acting gamma-aminobutyric acid type A (GABA(A)) agonist. Similar calming effects of 0.5 g/kg EtOH and 0.09 mg/kg MDZ were observed. Both drugs were then assessed in their capability to alter the expression of a conditioned aversion by devaluing the US. Aversive conditioning was conducted on postnatal day 14 (PD14) by pairing a lemon odor (conditioned stimulus, CS) with intraoral stimulation of citric acid (US). Control animals experienced both stimuli in an explicitly unrelated fashion. On PD15, pups were briefly exposed to the citric acid solution under the effects of 0.5 g/kg EtOH, 0.09 mg/kg MDZ, or the respective vehicle for each drug. Pups were then tested in a two-way odor preference test (lemon vs. cineole). Both vehicle- and MDZ-treated animals spent significantly less time near the lemon CS, thus expressing a citric acid-mediated odor aversion. This conditioned response was completely inhibited in pups that received 0.5 g/kg EtOH. Locomotor patterns at test were not affected by either EtOH or MDZ administration. A higher dose of MDZ (0.18 mg/kg, intraperitoneal) was also ineffective in attenuating the aversive memory. In summary, EtOH's devaluating capabilities are not shared by MDZ, indicating that these effects of EtOH may not be GABA mediated. Appetitive motivational properties of EtOH or non-GABA(A)-mediated antianxiety effects [i.e., N-methyl-D-aspartic acid (NMDA) related] could underlie this devaluation effect of EtOH.     

Periodicity of chronic ethanol administration as a variable in the induction of dependence in rats

The effect of periodicity of chronic ethanol intragastric administrations on the induction of physical and behavioral dependence on ethanol has been assessed in two groups of rats. In the two groups, rats initially selected for an identical sensitivity to ethanol, were administered daily 10 g per kg b.w. during 15 days. In one group, this daily dose was administered in six intragastric pulses of 1.7 g/kg each, 3 hours apart. In the other group, the same 10 g/kg daily dose was administered in three pulses of 3.33 g/kg, 6 hours apart. In control rats determinations of blood ethanol level in these two treatment conditions showed that the daily area of blood alcohol was 2.5 times higher in the first condition than in the second one. After the 15 days of chronic forced administration, experimental rats were subjected during 6 days to an alternate eight hours single bottle presentation of 10% ethanol solution and water. In this final test of the induced behavioral dependence, rats chronically treated by small frequent doses, displayed the highest intake of ethanol solution versus water. It is concluded that periodicity of a chronic administration or intake of ethanol is an important parameter in the induction of dependence, and the frequent administration of a small daily dose distributed in higher and less frequent unitary administrations.     

Opioid antagonists block the acquisition of ethanol-mediated conditioned tactile preference in infant rats

It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age. Experiment 1 determined the parameters (i.e., dose, interval of conditioning) for assessing ethanol-mediated conditioning. Pups were then trained with differential Pavlovian conditioning (Experiments 2 and 3) in which ethanol intoxication (1.0–2.0 g/kg, intragastrically or intraperitoneally delivered) was paired with a tactile stimulus (sandpaper) while an alternative texture signaled the absence of ethanol's effects. Unpaired control conditions were also used. Tactile preferences were assessed after two conditioning sessions. Paired rats spent significantly more time on sandpaper than unpaired controls, an effect that was greater after intragastric administration of 1.0 than 2.0 g/kg ethanol. This effect was replicated in Experiments 4a and 4c and found to be inhibited by pretreatment with general (naloxone [NAL]) or specific (d-Pen-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 [CTOP] and naltrindole) opioid antagonists. Blood ethanol levels at conditioning were not altered by NAL (Experiment 4b). The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process.     

Restraint stress and exogenous corticosterone differentially alter sensitivity to the sedative-hypnotic effects of ethanol in inbred long-sleep and inbred short-sleep mice

Decreased sensitivity to ethanol is a genetically mediated trait implicated in susceptibility to developing alcoholism. Here, we explore genotype by environment differences in ethanol sensitivity. The relationship between acute- and repeated-restraint stress, corticosterone (CORT) levels, and sensitivity to sedative-hypnotic properties of ethanol was explored using inbred long-sleep (ILS) and inbred short-sleep (ISS) mice. In ILS mice, acute restraint decreased ethanol sensitivity at a 4.1g/kg dose, as measured by a decrease in the duration of loss of the righting reflex (LORE) and an increase in blood ethanol concentration at regain of the righting response (BECRR). Repeated restraint also decreased LORE duration, but had no effect on BECRR. In the ISS mice, there was no effect of acute restraint on either LORE duration or BECRR. However, repeated restraint increased ethanol sensitivity at a 4.1g/kg dose; with an increase in LORE duration, but a decrease in BECRR. Differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to restraint stress (as measured by plasma CORT) were also examined between genotypes. ILS mice displayed habituation to repeated restraint, whereas ISS mice did not. Lastly, the effect of enhanced CORT levels independent of psychological stress was examined for its effects on the sedative-hypnotic effects of ethanol. There were no effects of CORT pretreatment on LORE duration or BECRR in ILS mice compared to saline- or noninjected littermates. In contrast, ISS mice injected with CORT showed a decreased duration of LORE, but no effects on BECRR. These findings suggest that in addition to genetic susceptibility, environmental factors (e.g., restraint stress, exogenous CORT administration) also influence sensitivity to the sedative effects of ethanol through alteration of central nervous system sensitivity and pharmacokinetic parameters, and do so in a genotype-dependent manner.     

Current status of and factors associated with social isolation in the elderly living in a rapidly aging housing estate community

Objectives

The aim of this study was to examine social isolation development among elderly persons living in a rapidly aging housing estate community in terms of the frequency of activities of daily living outside the home and social contact with neighbors and to identify associated factors.

Methods

A self-administered questionnaire survey was conducted in 2007 (102 subjects) and 2010 (104 subjects) involving elderly residents living on a suburban housing estate. The data collected on the 87 subjects who responded to both surveys were analyzed. The survey investigated physical, psychological, and social factors regarded as being associated with social isolation. The subjects were divided into four social types according to the frequency of activities of daily living outside the home and social contact with neighbors. Multiple logistic regression analysis involved would-be-isolated and non-isolated groups as dependent variables and each factor as an independent variable.

Results

Isolated group subjects increased from 2.3 to 7.0 % during the study period, with the would-be-isolated group accounting for 33.7 % of the study population in both years. Factors strongly associated with the would-be-isolated group were a low subjective sense of well-being and socioeconomic status were identified in 2007, and an older age, low subjective sense of socioeconomic status, and no provision of emotional support in 2010.

Conclusions

The health condition and social well-being of the elderly on a rapidly aging housing estate community tended to decline, revealing that the number of isolated and would-be-isolated subjects is increasing. Taking preventive action against social isolation among the elderly population is essential, suggesting the need to combine community health promotion and social communication interventions and to develop programs aimed at providing opportunities for elderly persons to be emotional support providers.     

Exploring the linkage between greenness exposure and depression among Chinese people: Mediating roles of physical activity,stress and social cohesion and moderating role of urbanicity

Although a plethora of studies have investigated the association between green exposure and mental health in developed countries, it is only recently that academics and policymakers have paid attention to how this association works in rapidly urbanizing and developing countries. This study aims to explore biopsychosocial pathways linking residential greenness exposure to depression in the Chinese context using data from the 2016 wave of China Labour-force Dynamics Survey. Results from multilevel models along with mediation analysis show that exposure to residential greenness is negatively associated with depression, and that physical activity, stress and neighbourhood social cohesion altogether have a complete mediation effect on this association. Results from moderation analysis suggest that urbanicity moderates the relationship between greenness exposure and depression, and that the relationship is strongest at the upper level of urbanicity. Our findings suggest the necessity of increasing the provision of recreational green spaces and improving the quality of green spaces in Chinese less urbanized areas.