Deprivation Effect Research Articles

The shift in sensory eye dominance from short-term monocular deprivation exhibits no dependence on test spatial frequency

BackgroundStudies have shown that short-term monocular deprivation induces a shift in sensory eye dominance in favor of the deprived eye. Yet, how short-term monocular deprivation modulates sensory eye dominance across spatial frequency is not clear. To address this issue, we conducted a study to investigate the dependence of short-term monocular deprivation effect on test spatial frequency.MethodsTen healthy young adults (age: 24.7 ± 1.7 years, four males) with normal vision participated. We deprived their dominant eye with a translucent patch for 2.5 h. The interocular contrast ratio (dominant eye/non-dominant eye, i.e., the balance point [BP]), which indicates the contribution that the two eyes make to binocular combination, was measured using a binocular orientation combination task. We assessed if BPs at 0.5, 4 or 6 cycles/degree (c/d) change as a result of monocular deprivation. Different test spatial frequency conditions were conducted on three separate days in a random fashion.ResultsWe compared the BPs at 0.5, 4 and 6 c/d before and after monocular deprivation. The BPs were found to be significantly affected by deprivation, where sensory eye dominance shift to the deprived eye (F1.86, 16.76 = 33.09, P < 0.001). The changes of BP were consistent at 0.5, 4, and 6 c/d spatial frequencies (F2,18 = 0.15, P = 0.57).ConclusionThe sensory eye dominance plasticity induced by short-term deprivation is not dependent on test spatial frequency, suggesting it could provide a practical solution for amblyopic therapy that was concerned with the binocular outcome.

Alcohol solution strength preference predicts compulsive-like drinking behavior in rats.

Understanding compulsive drinking behavior is key to improving outcomes in the treatment of addiction. In the present study, we investigated compulsive-like drinking in alcohol-addicted rats using the alcohol deprivation effect (ADE) model of relapse behavior, which involves repeated deprivation and reintroduction phases; the latter approximate relapse. High-resolution longitudinal drinking and locomotor data were measured while rats (n= 30) underwent a four-bottle (water, 5%, 10%, 20% alcohol v/v) free-choice ADE paradigm. Alcohol bottles were adulterated with the bitter compound quinine during a reintroduction phase to test for compulsive behavior. We characterized how drinking and locomotor behavior during ADE + quinine differed from a regular ADE and how, at the individual level, behavioral parameters extracted from the regular ADE related to compulsive-like drinking. Associations of drinking with locomotor activity were also examined. In the ADE with quinine, we observed reduced consumption of alcohol and a shift to preference for stronger alcohol. Quinine acted by decreasing both the access size and frequency of drinking of 5% alcohol while increasing the frequency of consumption of 20% alcohol. Preference for higher alcohol concentrations prior to the quinine challenge was associated with greater compulsive-like drinking behavior; higher baseline consumption of 20% alcohol correlated with more drinking of quinine-adulterated solutions while high frequency and amount of 5% alcohol consumption at baseline were correlated with being more strongly affected by quinine. Associations between locomotor activity and drinking behavior were observed at the hourly level. These associations reflected changing preferences across experimental phases. Drinking patterns, and specifically solution preference, may offer insights into the presentation of compulsive-like drinking. The findings provide a preclinical basis for observations from epidemiological studies that link higher risk and burden of alcohol-related disease to stronger alcohol concentrations and encourage further translational studies to better understand the underlying mechanisms.

Gonadal hormones and sex chromosome complement differentially contribute to ethanol intake, preference, and relapse-like behaviour in four core genotypes mice.

Alcohol use and high-risk alcohol drinking behaviours among women are rapidly rising. In rodent models, females typically consume more ethanol (EtOH) than males. Here, we used the four core genotypes (FCG) mouse model to investigate the influence of gonadal hormones and sex chromosome complement on EtOH drinking behaviours. FCG mice were given access to escalating concentrations of EtOH in a two-bottle, 24-h continuous access drinking paradigm to assess consumption and preference. Relapse-like behaviour was measured by assessing escalated intake following repeated cycles of deprivation and re-exposure. Twenty-four-hour EtOH consumption was greater in mice with ovaries (Sry-), relative to those with testes, and in mice with the XX chromosome complement, relative to those with XY sex chromosomes. EtOH preference was higher in XX versus XY mice. For both consumption and preference, the influences of the Sry gene and sex chromosomes were concentration dependent. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). Mice with ovaries (Sry- FCG mice and C57BL/6J females) were also found to consume more water than mice with testes. These results demonstrate that aspects of EtOH drinking behaviour may be independently regulated by sex hormones and chromosomes and inform our understanding of the neurobiological mechanisms which contribute to EtOH dependence in male and female mice. Future investigation of the contribution of sex chromosomes to EtOH drinking behaviours is warranted. We used the FCG mouse model to investigate the influence of gonadal hormones and sex chromosome complement on EtOH drinking behaviours, including the alcohol deprivation effect. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). These results demonstrate that aspects of EtOH drinking behaviour may be independently regulated by sex hormones and chromosomes.

The Mechanism of Short-Term Monocular Pattern Deprivation-Induced Perceptual Eye Dominance Plasticity.

Previously published studies have reported that 150 min of short-term monocular deprivation temporarily changes perceptual eye dominance. However, the possible mechanisms underlying monocular deprivation-induced perceptual eye dominance plasticity remain unclear. Using a binocular phase and contrast co-measurement task and a multi-pathway contrast-gain control model (MCM), we studied the effect of 150 min of monocular pattern deprivation (MPD) in normal adult subjects. The perceived phase and contrast varied significantly with the interocular contrast ratio, and after MPD, the patched eye (PE) became dominant. Most importantly, we focused on the potential mechanisms of the deprivation effect. The data of an averaged subject was best fitted by a model, which assumed a monocular signal enhancement of the PE after the MPD. The present findings might have important implications for investigations of binocular vision in both normal and amblyopic populations.

A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player

RationaleGut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the “alcohol deprivation effect” where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition. MethodsRats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+ (NAC/ASA). ResultsMarked binge drinking (1.75 g ethanol/kg in 60 min) and blood alcohol levels exceeding 80 mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66–80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT). ConclusionsThe administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders.

Alcohol Deprivation Differentially Changes Alcohol Intake in Female and Male Rats Depending on Early-Life Stressful Experience.

Experiencing early-life adverse events has enduring effects on individual vulnerability to alcohol abuse and the development of addiction-related behaviors. In rodents, it can be studied using maternal separation (MS) stress. Studies have shown that, depending on the protocol used, MS can affect the mother and pups' behavior and are associated with behavioral alterations later in adulthood, associated with both positive or negative outcomes. However, it is not fully elucidated how MS affects relapse-like behaviors when experienced by female or male individuals. Therefore, the aim of our study was to evaluate the effects of brief and prolonged MS on the alcohol deprivation effect (ADE) in female and male rats. Female and male Wistar rats were exposed to brief (15 min/day) or prolonged (180 min/day) MS from postnatal day (PND) 2 to 10. Later, during adulthood (PND 70), animals were submitted to an ADE protocol. Brief MS exposure prevented the ADE in both females and males, while prolonged MS exposure also prevented the ADE in female rats. Moreover, the ADE was more robust in females when compared to males. In conclusion, we showed that male and female rats are differentially affected by alcohol deprivation periods depending on their early-life experiences.

Maternal deprivation effect on morphine-induced CPP is related to changes in opioid receptors in selected rat brain regions (hippocampus, prefrontal cortex, and nucleus accumbens)

Early-life environmental conditions affect offspring's development. Maternal deprivation (MD) can induce persistent changes that give rise to neuropsychiatric diseases including substance abuse disorders. However, long-lasting mechanisms that determine vulnerability to drug addiction remain unknown. We hypothesized that MD could induce changes in Opioid system, HPA (hypothalamic-pituitary-adrenal) axis, and BDNF (brain-derived neurotrophic factor), so may be involved in the drug abuse in later life. Male offspring of Wistar rats (n = 8 per group) were subjected to 3 h of daily MD during postnatal days 1–14. In adulthood, morphine-induced CPP (conditioned place preference) was investigated using two doses of morphine (3 and 5 mg/kg). Serum corticosterone level was measured by ELISA method. The expression level of genes in selected brain regions (hippocampus, prefrontal cortex, and nucleus accumbens) was determined by qPCR (quantitative PCR). A greater morphine-induced CPP was observed in MD rats with 3 and 5 mg/kg morphine compared to controls. MD group had a higher corticosterone level. A significant decrease was observed in the expression of BDNF gene (in all of the selected brain regions) and GR (glucocorticoid receptor) gene (in the hippocampus and nucleus accumbens) in MD rats. Also, a significant increase in the expression of μ Opioid receptor (in all of the selected brain regions) and κ Opioid receptor (in the prefrontal cortex and nucleus accumbens) was observed in MD rats. Our results suggest that MD induces alterations in the HPA axis function, BDNF level, and Opioid receptors system that enhance vulnerability to morphine at adulthood.

Different brain oxidative and neuroinflammation status in rats during prolonged abstinence depending on their ethanol relapse-like drinking behavior: Effects of ethanol reintroduction

RationaleAccumulating evidence suggests that chronic alcohol consumption is associated with excessive oxidative damage and neuroinflammatory processes and these events have been associated to early alcohol withdrawal. In the present research we wonder if brain oxidative stress and neuroinflammation remains altered during prolonged withdrawal situations and whether these alterations can be correlated with relapse behavior in alcohol consumption. The effects of alcohol reintroduction were also evaluated MethodsWe have used a model based on the alcohol deprivation effect (ADE) within a cohort of wild-type male Wistar rats. Two subpopulations were identified according to the alcohol relapse-like drinking behavior displayed (ADE and NO-ADE subpopulations). Oxidized and reduced glutathione content was determined within the hippocampus and the amygdala using a mass spectrometry method. The levels of mRNA of seven different inflammatory mediators in the prefrontal cortex of rats were quantified. All the analyses were performed in two different conditions: after 21-day alcohol deprivation (prolonged abstinence) and after 24 h of ethanol reintroduction in both subpopulations. ResultsADE and NO-ADE rats showed different endophenotypes. ADE rats always displayed a significant lower alcohol intake rate and ethanol preference than NO-ADE rats. The results also demonstrated the existence of altered brain redox and neuroinflammation status after prolonged abstinence exclusively in ADE rats. Moreover, when ethanol was reintroduced in the ADE subpopulation, altered oxidative stress and neuroinflammatory markers were restored. ConclusionsPresent findings provide new mechanisms underlying the neurobiology of relapse behavior and suggest the development of new pharmacological approaches to treat alcohol-induced relapse.

Aticaprant (Clinically Developed Kappa-Opioid Receptor Antagonist) Combined With Naltrexone Prevents Alcohol "Relapse" Drinking.

Alcohol relapse is the treatment target for medications development for alcohol dependence. Aticaprant, a selective and short-acting kappa-opioid receptor (KOR) antagonist, has recently been under development for new clinical implications (depression or anhedonia). Recent studies have also found that aticaprant reduces alcohol intake and prevents stress- triggered alcohol seeking in rodents via a KOR-mediated mechanism. Here, we further investigated whether aticaprant alone or in combination with naltrexone (mu-opioid receptor [MOR] antagonist) altered alcohol relapse-like drinking using a mouse alcohol deprivation effect (ADE) paradigm to mimic the relapse episodes in human alcoholics. A long-acting and selective KOR antagonist nor-BNI was used as a reference compound for the effects of the KOR antagonism on the ADE. After 3-week intermittent-access alcohol drinking (two-bottle choice, 24-h access every other day), male and female mice displayed excessive alcohol intake and then pronounced ADE after 1-week abstinence. Aticaprant alone decreased alcohol ADE in a dose- dependent manner (1–3 mg/kg) in both males and females. Aticaprant at a lower dose (0.3 mg/kg) than the effective one (3 mg/kg) combined with a low dose of naltrexone (1 mg/kg) reduced the ADE in both sexes, and the combination was effective after a multi-dosing regimen (5 daily injections during the abstinence) without development of tolerance, suggesting synergistic effects of the combination. In contrast, nor-BNI alone or with naltrexone had no effect on the ADE in either sex. Our present study suggests that a combination of clinically developed, short-acting KOR antagonist aticaprant with low-dose naltrexone has therapeutic potential in alcohol “relapse” treatment.

Effects of sex and genotype in human APOE-targeted replacement mice on alcohol self-administration measured with the automated IntelliCage system before and after repeated mild traumatic brain injury.

Few studies have examined the association between APOE genotype and alcohol use. Although some of these studies have reported outcomes associated with a history of drinking, none have examined alcohol-seeking behavior. In addition, no preclinical studies have examined alcohol use as a function of APOE genotype with or without traumatic brain injury. Male and female human APOE3- and APOE4-targeted replacement (TR) mice were used to assess voluntary alcohol seeking longitudinally using a 2-bottle choice paradigm conducted within the automated IntelliCage system prior to and following repeated mild TBI (rmTBI). Following an acquisition phase in which the concentration of ethanol (EtOH) was increased to 12%, a variety of drinking paradigms that included extended alcohol access (EAA1 and EAA2), alcohol deprivation effect (ADE), limited access drinking in the dark (DID), and progressive ratio (PR) were used to assess alcohol-seeking behavior. Additional behavioral tasks were performed to measure cognitive function and anxiety-like behavior. All groups readily consumed increasing concentrations of EtOH (4-12%) during the acquisition phase. During the EAA1 period (12% EtOH), there was a significant genotype effect in both males and females for EtOH preference. Following a 3-week abstinence period, mice received sham or rmTBI resulting in a genotype- and sex-independent main effect of rmTBI on the recovery of righting reflex and a main effect of rmTBI on spontaneous home-cage activity in females only. Reintroduction of 12% EtOH (EAA2) resulted in a significant effect genotype for alcohol preference in males with APOE4mice displaying increased preference and motivation for alcohol compared with APOE3mice independent of TBI while in females, there was a significant genotype×TBI interaction under the ADE and DID paradigms. Finally, there was a main effect of rmTBI on increased risk-seeking behavior in both sexes, but no effect on spatial learning or cognitive flexibility. These results suggest that sex and APOE genotype play a significant role in alcohol consumption and may subsequently influence long-term recovery following traumatic brain insults.

Modulation of relapse-like drinking in male Sprague-Dawley rats by ligands targeting the α5GABAA receptor

Preclinical evidence suggests a key role for GABAA receptors containing the α5 subunit (i.e., α5GABAA receptors) in the abuse-related effects of alcohol, including the reinforcing and discriminative stimulus effects, as well as cue-induced alcohol-seeking behavior. However, the contribution of this GABAA receptor subtype to relapse-like drinking behavior remains unknown. The present study evaluated the capacity of ligands targeting α5GABAA receptors to modulate the alcohol deprivation effect (ADE), a model of relapse-like drinking. Groups of Sprague-Dawley rats underwent repeated cycles of long-term access to alcohol solutions (5%, 10%, 20% v/v) and water in the home cage followed by water only deprivation periods. Upon evidence that the ADE could be reliably expressed across cycles, drug treatment was initiated. One group received the α5GABAA receptor-preferring agonist QH-ii-066 and the other group received the α5GABAA receptor-selective inverse agonist L-655,708. At the end of ADE testing, rats underwent testing in the elevated zero maze under vehicle or L-655,708 treatment for assessment of anxiety-like behavior. The ADE was reliably expressed across repeated cycles of alcohol access/deprivation in a subset of rats. Low doses of QH-ii-066 enhanced expression of the ADE; whereas, L-655,708 dose-dependently inhibited expression of the ADE. L-655,708 did not engender anxiogenic effects in the elevated zero maze under the conditions evaluated. These findings suggest a key role for α5GABAA receptor mechanisms in relapse-like drinking. Moreover, they suggest that α5GABAA receptors may represent a novel pharmacological target for the development of medications to prevent or reduce alcohol relapse.

Low-Molecular-Weight Mimetic of BDNF Loop 2 Reduces Ethanol Consumption in Female Rats.

The study examined the effect of GTS-201, a low-molecular weight mimetic of brain-derived neurotrophic factor (BDNF) loop 2, on persistent alcohol craving in outbred male and female albino rats with ethanol preference score ~50% developed in the free choice paradigm between 10% ethanol and water over 24 weeks. Both single and subchronic (5 days) injections of GTS-201 in a daily dose of 5 μg/kg reduced alcohol deprivation effect in female, but not in male rats. The possibility of in vivo sex-dependent regulation of modeled alcohol craving with a low-molecular-weight dipeptide mimetic of BDNF loop 2 was demonstrated and sex-related differences in this effect were revealed.

Long-term alcohol drinking in High Drinking in the Dark mice is stable for many months and does not show alcohol deprivation effects.

We have modelled genetic risk for binge-like drinking by selectively breeding High Drinking in the Dark-1 and -2 (HDID-1 and HDID-2) mice for their propensity to reach intoxicating blood alcohol levels (BALs) after binge-like drinking in a single bottle, limited access paradigm. Interestingly, in standard two-bottle choice (2BC) tests for continuously available alcohol versus water, HDID mice show modest levels of preference. This indicates some degree of independence of the genetic contributions to risk for binge-like and sustained, continuous access drinking. We had few data where the drinking in the dark (DID) tests of binge-like drinking had been repeatedly performed, so we serially offered multiple DID tests to see whether binge-like drinking escalated. It did not. We also asked whether HDID mice would escalate their voluntary intake with prolonged exposure to alcohol 2BC. They did not. Lastly, we assessed whether an alcohol deprivation effect (ADE) developed. ADE is a temporary elevation in drinking typically observed after a period of abstinence from sustained access to alcohol choice. With repetition, these periods of ADE sometimes have led to more sustained elevations in drinking. We therefore asked whether repeated ADE episodes would elevate choice drinking in HDID mice. They did not. After nearly 500 days of alcohol access, the intake of HDID mice remained stable. We conclude that a genetically-enhanced high risk for binge-like drinking is not sufficient to yield alterations in long-term alcohol intake.

Racial and Ethnic Disparities in Hospital Admissions from COVID-19: Determining the Impact of Neighborhood Deprivation and Primary Language.

BackgroundDespite past and ongoing efforts to achieve health equity in the USA, racial and ethnic disparities persist and appear to be exacerbated by COVID-19.ObjectiveEvaluate neighborhood-level deprivation and English language proficiency effect on disproportionate outcomes seen in racial and ethnic minorities diagnosed with COVID-19.DesignRetrospective cohort studySettingHealth records of 12 Midwest hospitals and 60 clinics in Minnesota between March 4, 2020, and August 19, 2020PatientsPolymerase chain reaction–positive COVID-19 patientsExposuresArea Deprivation Index (ADI) and primary languageMain MeasuresThe primary outcome was COVID-19 severity, using hospitalization within 45 days of diagnosis as a marker of severity. Logistic and competing-risk regression models assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race, effects of ADI and primary language were measured using logistic regression.ResultsA total of 5577 individuals infected with SARS-CoV-2 were included; 866 (n = 15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p < 0.001) and more likely to be male (n = 425 [49.1%] vs. 2049 [43.5%], p = 0.002). Of those requiring hospitalization, 43.9% (n = 381), 19.9% (n = 172), 18.6% (n = 161), and 11.8% (n = 102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity: Hispanic patients (OR 3.8, 95% CI 2.72–5.30), Asians (OR 2.39, 95% CI 1.74–3.29), and Blacks (OR 1.50, 95% CI 1.15–1.94). ADI was not associated with hospitalization. Non-English-speaking (OR 1.91, 95% CI 1.51–2.43) significantly increased odds of hospital admission across and within minority groups.ConclusionsMinority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the ongoing need to determine the mechanisms that contribute to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity among minority groups.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06790-w.

Kappa opioid receptor blockade in the nucleus accumbens shell prevents sex-dependent alcohol deprivation effect induced by inflammatory pain.

Pain-induced negative affect reduces life quality of patients by increasing psychiatric comorbidities, including alcohol use disorders (AUDs). Indeed, clinical data suggest pain as a risk factor to suffer AUDs, predicting relapse drinking in abstinent patients. Here, we analyse the impact of pain on alcohol relapse and the role of kappa opioid receptor (KOR) activation in mediating these pain-induced effects because KORs play an important role in pain-driven negative affect and AUD. Female and male Sprague-Dawley rats underwent 2 alcohol intermittent access periods separated by a forced abstinence period. The complete Freund adjuvant model of inflammatory pain was introduced during abstinence, and alcohol intake before and after alcohol reintroduction was assessed. In addition, we used behavioural approaches to measure stress and memory impairment and biochemical assays to measure KOR expression in abstinence and reintroduction periods. Only female CFA-treated rats increased alcohol intake during the reintroduction period. Concomitantly, this group showed enhanced anxiety-like behaviour and increased KOR expression in the nucleus accumbens shell that was developed during abstinence and remained during the reintroduction period. Finally, KOR antagonist norbinaltorphimine was administered in the nucleus accumbens shell during abstinence to prevent a pain-induced alcohol deprivation effect, a phenomenon observed in CFA-female rats. The administration of norbinaltorphimine effectively blocked a pain-induced alcohol deprivation effect in female rats. Our data evidenced that inflammatory pain constitutes a risk factor to increase alcohol consumption during a reintroduction phase only in female rats by the rise and maintenance of stress probably mediated by KOR signalling in the nucleus accumbens.

Female mice are more prone to develop an addictive-like phenotype for sugar consumption

The concept of “sugar addiction” is gaining increasing attention in both the lay media and scientific literature. However, the concept of sugar addiction is controversial and only a few studies to date have attempted to determine the “addictive” properties of sugar using rigorous scientific criteria. Here we set out to systematically test the addictive properties of sugar in male and female mice using established paradigms and models from the drug addiction field. Male and female C57BL/6N (8–10 weeks old) were evaluated in 4 experimental procedures to study the addictive properties of sugar: (i) a drinking in the dark (DID) procedure to model sugar binging; (ii) a long-term free choice home cage drinking procedure measuring the sugar deprivation effect (SDE) following an abstinence phase; (iii) a long-term operant sugar self-administration with persistence, motivation and compulsivity measures and (iv) intracranial self-stimulation (ICSS). Female mice were more vulnerable to the addictive properties of sugar than male mice, showing higher binge and long-term, excessive drinking, a more pronounced relapse-like drinking following deprivation, and higher persistence and motivation for sugar. No sex differences were seen in a compulsivity test or reward sensitivity measured using ICSS following extended sugar consumption. This study demonstrates the occurrence of an addictive-like phenotype for sugar in male and female mice, similar to drugs of abuse, and suggests sex-dependent differences in the development of sugar addiction.

Social preference in rats.

Rats were given repeated choices between social and nonsocial outcomes, and between familiar and unfamiliar social outcomes. Lever presses on either of 2 levers in the middle chamber of a 3-chamber apparatus opened a door adjacent to the lever, permitting 45-s access to social interaction with the rat in the chosen side chamber. In Experiment 1, rats preferred (a) social over nonsocial options, choosing their cagemate rat over an empty chamber, and (b) an unfamiliar over a familiar rat, choosing a non-cagemate over their cagemate. These findings were replicated in Experiment 2 with 2 different non-cagemate rats. Rats preferred both non-cagemate rats to a similar degree when pitted against their cagemate, but were indifferent when the 2 non-cagemates were pitted against each other. Similar preference for social over nonsocial and non-cagemate over cagemate was seen in Experiment 3, with new non-cagemate rats introduced after every third session. Response rates (for both cagemate and non-cagemate rats) were elevated under conditions of nonsocial (isolated) housing compared to conditions of social (paired) housing, demonstrating a social deprivation effect. Together, the experiments contribute to an experimental analysis of social preference within a social reinforcement framework, drawing on methods with proven efficacy in the analysis of reinforcement more generally.

The ups and downs of sensory eye balance: Monocular deprivation has a biphasic effect on interocular dominance

Classic studies of ocular dominance plasticity in early development showed that monocular deprivation suppresses the neural representation and visual function of the deprived eye. However, recent studies have shown that a short period of monocular deprivation (<3 h) in normal adult humans, shifts sensory eye dominance in favor of the deprived eye. How can these opposing effects be reconciled? Here we argue that there are two systems acting in opposition at different time scales. A fast acting, stabilizing, homeostatic system that rapidly decreases gain in the non-deprived eye or increases gain in the deprived eye, and a relatively sluggish system that shifts balance toward the non-deprived eye, in an effort to reduce input of little utility to active vision. If true, then continuous deprivation should produce a biphasic effect on interocular balance, first shifting balance away from the non-deprived eye, then towards it. Here we investigated the time course of the deprivation effect by monocularly depriving typical adults for 10 h and conducting tests of sensory eye balance at six intervening time points. Consistent with previous short-term deprivation work, we found shifts in sensory eye dominance away from the non-deprived eye up until approximately 5 h. We then observed a turning point, with balance shifting back towards the non-deprived eye, -, a biphasic effect. We argue that this turning point marks where the rapid homeostatic response saturates and is overtaken by the slower system responsible for suppressing monocular input of limited utility.

The Effect of Monaurally Fitted Hearing Aid Use on the Evolution of Presbycusis.

The effect of hearing aid use on the evolution of presbycusis has not been well described in the literature, with only a handful of publications addressing this topic. This paper aims to evaluate the long-term use of amplification and its effect on pure-tone thresholds and word recognition scores. Monaurally fitted patients were followed with serial audiograms. Data was collected from hearing aid centers. Seventy-seven patients with presbycusis met the inclusion criteria and participated in the present study. The progression of hearing loss in both pure tone thresholds and word recognition scores were compared between the hearing aid ears (HA), and the non-hearing aid ears (NHA). Pure tone thresholds were analyzed by comparing the pure tone average at the initial and last audiograms. Word Recognition Scores (WRS) were analyzed using the model of Thornton and Raffin (1978), and by comparing the change in the absolute values of WRS from the initial to the last audiogram between the HA ear and the NHA ear. No significant difference in pure-tone thresholds between the HA ear and NHA ear was found at the last audiogram (P = .696), even after dividing the patients into groups based on the duration of amplification. Both methods of analysis of patients' WRS showed a statistically significant worsening in NHA (P < .05). The present study supports the previously defined auditory deprivation effect on non-fitted ears, which showed worsening of word recognition over time and no effect on pure tone average. It provides an additional argument for the counseling of patients with presbycusis considering amplification, and highlights the importance of bilateral amplification in preserving the residual hearing of hearing impaired patients.

Blockade of alcohol excessive and "relapse" drinking in male mice by pharmacological cryptochrome (CRY) activation.

Metabolic dysfunction, mood disorders, anxiety disorders, and substance abuse disorders are associated with disruptions in circadian rhythm and circadian clock gene machinery. While the effects of alcohol on several core components of the clock genes have been described in rodent models, pharmacological activation or inhibition of clock gene functions has not been studied on alcohol drinking behaviors. We investigated whether cryptochrome (CRY1/2) activator KL001 altered alcohol intake in mice in excessive and relapse-like alcohol drinking models. Mice, subjected to 3 weeks of chronic intermittent alcohol drinking (IAD) (two-bottle choice, 24-h access every other day) developed excessive alcohol intake and high preference. We evaluated the pharmacological effects of KL001 after either 1-day acute withdrawal from IAD or 1-week chronic withdrawal using the alcohol deprivation effect (ADE) model. Single pretreatment with KL001 at 1-4 mg kg-1 reduced alcohol intake and preference after acute withdrawal in a dose-related manner. The effect of KL001 on reducing excessive alcohol consumption seems alcohol specific, as the compound does not alter sucrose (caloric reinforcer) or saccharin (noncaloric reinforcer) consumption in mice. Both single- and multiple-dosing regimens with an effective dose of KL001 (4 mg kg-1) prevented the ADE after chronic withdrawal, with no tolerance development after the multi-dosing regimen. Pretreatment with KL001 (a CRY1/2 activator) reduces excessive and "relapse" alcohol drinking in mice. Our in vivo results with a CRY activator suggest a possible novel target for alcohol treatment intervention.