Sex differences in the social motivation of rats: Insights from social operant conditioning, behavioural economics, and video tracking.

BACKGROUND: Social behaviour plays a key role in mental health and wellbeing, and developing greater understanding of mechanisms underlying social interaction-particularly social motivation-holds substantial transdiagnostic impact. Common rodent behavioural assays used to assess social behaviour are limited in their assessment of social motivation, whereas the social operant conditioning model can provide unique and valuable insights into social motivation. Further characterisation of common experimental parameters that may influence social motivation within the social operant model, as well as complementary methodological and analytical approaches, are warranted. METHODS: This study investigated the effects of biological sex, housing condition, and time-of-day, on social motivation using the social operant model. This involved training rats to lever press (FR1) for 60-s access to a social reward (same-sex conspecific stimulus). Subjects were male and female Wistar rats, housed under individual or paired conditions, and sessions were conducted either in the mid-late light phase (ZT6-10) or early-mid dark phase (ZT13-17). A behavioural economics approach was implemented to measure social demand and the influence of stimulus partner sex (same- vs. opposite-sex stimulus) on social operant responding. Additionally, video tracking analyses were conducted to assess the degree of convergence between social appetitive and consummatory behaviours. RESULTS: Biological sex, housing conditions, the interaction between sex and housing, and stimulus partner sex potently influenced social motivation, whereas time-of-day did not. Behavioural economics demonstrated that sex, housing, and their interaction influence both the hedonic set-point and elasticity of social demand. Video analysis of social interaction during social operant sessions revealed that social appetitive and consummatory behaviours are not necessarily convergent, and indicate potential social satiety. Lastly, oestrus phase of female experimental and stimulus rats did not impact social motivation within the model. CONCLUSIONS: Social isolation-dependent sex differences exist in social motivation for rats, as assessed by social operant conditioning. The social operant model represents an optimal preclinical assay that comprehensively evaluates social motivation and offers a platform for future investigations of neurobiological mechanisms underlying sex differences in social motivation. These findings highlight the importance of continued consideration and inclusion of sex as a biological variable in future social operant conditioning studies. Humans are social creatures-our everyday interactions with others and the support this provides play a key role in our wellbeing. For those experiencing mental health conditions, people's motivation to engage with others can wane, which can lead them to withdraw from those who support them. Therefore, to develop better treatment strategies for these conditions, we need to gain a deeper understanding of social motivation. Studying social behaviour in animals can facilitate this investigation of social motivation as it allows for a causal understanding of underlying neurobiology that is not possible in human experiments. An optimal way to study social motivation in animals is using the social operant conditioning model, where rats learn to press a lever that opens a door and allows them to interact with another rat for a short time. This study characterised the social operant model by testing whether sex, housing conditions, time-of-day, and the sex of the stimulus partner influence rats' motivation to seek interaction with another rat. We found that female rats were more socially motivated than males, and that rats living alone were more motivated than those living with another rat; interestingly, this effect of housing affected females more than males. Regardless of sex, rats were more motivated to interact with a rat of the opposite sex. These findings provide insights into sex differences in social motivation in rats and new insights into the social operant model which will help guide future research into social motivation and other mental health conditions.

Taste aversion learning during successive negative contrast.

Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This study tested whether such successive negative contrast (SNC) effects involve acquisition of an aversion to the new taste. In three experiments, rats were switched from sucrose exposure in Stage 1 to a less palatable solution containing a new taste in Stage 2. In Experiments 1 and 2, a novel flavor was added to a saccharin solution at the start of Stage 2. In Experiment 1, preference tests revealed a weak aversion to the added vanilla flavor in the Suc-Sacch group, while in Experiment 2 an aversion was found in the Suc-Sacch group to the salty flavor that was used, compared with controls given access either saccharin or water in Stage 1. In Experiment 3, the Suc-Quin group, given quinine solution in Stage 2, displayed a greater aversion to quinine than a Water-Quin control group. These results support the suggestion that taste aversion learning plays a role in the initial suppression of intakes in a qualitative consummatory SNC effect. However, in the light of other evidence, it seems that the unusual persistence of successive negative contrast when rats are switched from sucrose to saccharin is not due to a long-lasting reduction in the value of saccharin.

Switching from sucrose to saccharin: Extended successive negative contrast is not maintained by hedonic changes.

Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This reduction in saccharin consumption was particularly extended after a switch from sucrose. On the surface, this seems to correspond to a successive negative contrast (SNC) effect. This term was coined by C. F. Flaherty to describe the situation where consumption of a target solution is reduced by prior experience of a more valuable solution, typically a more concentrated version of the target solution. However, SNC effects are normally transient and assessed relative to a nonshifted control. Here, we confirm that the reduction in consumption seen when shifting from sucrose to saccharin is persistent and is seen relative to the traditional unshifted control. In addition, an analysis of licking microstructure showed that the shift from sucrose to saccharin suppressed the hedonic value of saccharin relative to controls, but this effect was less persistent than consumption suppression. Interestingly, a similar dissociation is observed in extinction of conditioned taste aversion (CTA): suppression of consumption produced by CTA is far more persistent than suppression of hedonic value. The comparison of results across procedures suggests that persistent SNC produced by a qualitative downshift from sucrose to saccharin appears different from quantitative downshifts in the concentration of a single solution, and qualitative downshift effects may involve CTA. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day.

RATIONALE: Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin's effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored. OBJECTIVES: This study examined the role of entrainment on intake patterns, oxytocin's effects on sucrose intakes and locomotor activity and whether oxytocin's effects were mediated by its actions at the oxytocin receptor. METHODS: Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access. RESULTS: Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear. CONCLUSIONS: Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

Laboratory animals search filter for different literature databases: PubMed, Embase, Web of Science and PsycINFO.

Systematic reviews are important tools in animal research, but the ever-increasing number of studies makes retrieval of all relevant publications challenging. Search filters aid in retrieving as many animal studies as possible. In this paper we provide updated and expanded versions of the SYRCLE animal filters for PubMed and Embase. We provide the Embase filter for both Embase.com and via Ovid. Furthermore, we provide new animal search filters for Web of Science (WoS) and APA PsycINFO via psycnet.apa.org and via Ovid. Compared with previous versions, the new filters retrieved 0.5-47.1% (19 references for PubMed, 837 for WoS) more references in a real-life example. All filters retrieved additional references, comprising multiple relevant reviews. A random sample from WoS found at least one potentially relevant primary study. These animal search filters facilitate identifying as many animal studies as possible while minimising the number of non-animal studies.

A systematic review and meta-analysis of animal models of binge eating - Part 1: Definitions and food/drink intake outcomes.

Binge eating involves consuming excessive amounts of food within a discrete period of time and is associated with significant impairments in binge-eating disorder and bulimia nervosa. While research on clinical binge eating has provided valuable aetiological insights, animal models allow for closer examination of environmental, biological, and developmental risk factors. Numerous animal models of binge eating exist and differ widely in operational definitions of bingeing, animal characteristics and methodological parameters. The current review aimed to synthesise the available published evidence on these models. A systematic review of binge definitions in 170 articles found most studies displayed good face validity. Meta-analyses on 150 articles confirmed that the amount of food or drink consumed by animals under binge conditions was larger than that of non-binge conditions across many protocols. The meta-regression revealed species, strain, and sex moderated binge effect size, with the largest effect observed in studies with female animals and mice. Risk of bias assessment identified that improved reporting of allocation, baseline characteristics and outcome assessment is required in future studies.

Caffeine-based flavor preference conditioning in the rat.

The massive consumption of caffeine-containing beverages has prompted many studies involving human participants that have obtained caffeine-based increases in liking for a flavor. However, few studies have succeeded in obtaining caffeine-based flavor preference learning in rats. The main aim of the present study was to examine the conditions under which such learning can be detected. Three experiments differed mainly in terms of the base solution to which caffeine was added. Using a base of maltodextrin and saccharin, Experiment 1 found modest increases in flavor preferences in both food- and fluid-restricted rats. Experiment 2 found a strong caffeine-based flavor preference when water, but not saccharin, was used as the base. Whereas the first two experiments used a within-subject design, in which one flavor was paired with caffeine and a second flavor was not, Experiment 3 used a between-subject design with fluid-restricted rats given almond-flavored water containing caffeine in the Paired condition but not in the Unpaired condition; caffeine-based flavor preference learning was again found. In Experiments 1 and 2 post-conditioning exposure to the flavor alone produced a decrease in preference. In summary, the main achievements of this study were to extend the conditions under which caffeine-based flavor preferences can be detected in rats and demonstrate that such learned preferences are subject to extinction.

The influence of oxytocin-based interventions on sleep-wake and sleep-related behaviour and neurobiology: A systematic review of preclinical and clinical studies.

The oxytocin (OXT) system has garnered considerable interest due to its influence on diverse behaviours. However, scant research has considered the influence of oxytocin on sleep-wake and sleep-related behaviour and neurobiology. Consequently, the objective of this systematic review was to assess the extant preclinical and clinical evidence for the influence of oxytocin-based interventions on sleep-wake outcomes. The primary search was conducted on 22/7/2020 using six electronic databases; 30 studies (19 preclinical, 11 clinical) were included based on inclusion criteria. Studies were evaluated for risk of bias using the SYRCLE tool and the Cochrane risk of bias tools for preclinical and clinical studies, respectively. Results indicated manipulation of the OXT system can influence sleep-wake outcomes. Preclinical evidence suggests a wake-promoting influence of OXT system activation whereas the clinical evidence suggests little or no sleep-promoting influence of OXT. OXT dose was identified as a likely modulatory factor of OXT-induced effects on sleep-wake behaviour. Future studies are necessary to validate and strengthen these tentative conclusions about the influence of OXT on sleep-wake behaviour.

Sex differences in recovery from cognitive and metabolic impairments induced by supplementary sucrose in rats.

Consumption of beverages containing around 10% sucrose contributes to worldwide obesity. Studies using rats can increase understanding of the consequences of such consumption. The present experiment aimed to compare male and female rats, first, in terms of cognitive and metabolic impairments produced by excessive intakes of 10% sucrose solution (Stage 1:8 weeks) and, second, with regard to recovery once access to sucrose ceased (Stage 2:4 weeks). All animals had unrestricted access to chow and water throughout. The primary cognitive outcome was performance on a place recognition task. The primary metabolic outcome was retroperitoneal fat pad mass/kg bodyweight at cull, with body weight and glucose tolerance as secondary outcomes. In a 3 × 2 between-subject factorial design the first factor was whether rats had: (1) unlimited access to a 10% sucrose solution and water throughout both stages (Suc-Suc); (2) were switched from sucrose in the 8-week Stage 1 to water only in the 4-week Stage 2 (Suc-Water); or (3) had no access to sucrose in either stage (Water-Water). The second factor was sex. A major metabolic outcome was that of persistent adiposity in both males and females in the Suc-Water condition. As for place recognition, females in the Suc-Suc condition showed greater long-term resistance than males to the impact of excessive sucrose on spatial memory impairment. Overall, few sex differences were found in secondary metabolic outcomes.

Reduced acceptance of saccharin solutions by rats previously consuming more highly palatable solutions.

Rats first given 24-h access to 10% sucrose for 4 or 12 days (Stage 1) were then switched to a saccharin solution for a 12-day Stage 2. The initial result of this switch was that these Sucrose groups drank less saccharin than Water groups that had been given only water to drink in Stage 1. This difference was maintained throughout Stage 2 by the females that served in Experiments 1 and 4 and by the males that served in Experiment 3. Experiment 1 also found that access to 10% glucose in Stage 1 produced an essentially identical decrease in subsequent saccharin acceptance as that produced by giving 10% sucrose in Stage 1. The impact on subsequent acceptance of saccharin was also tested in rats given two types of maltodextrin solution. The first type of maltodextrin (Myopure brand) was used with the males in Experiment 2; this failed to find any difference between the Maltodextrin and the Water group. However, when a second type of maltodextrin (SolCarb brand) was given to males in Stage 1 of Experiment 3, the results for this group were similar to those from a group given sucrose in Stage 1. The final experiment confirmed that prior exposure to maltodextrin solutions can reduce saccharin acceptance by female rats. Overall, the results suggest that acceptance of saccharin is sensitive to a contrast effect, in that it is reduced by prior exposure to a solution that is more palatable but not necessarily sweet.

Bingeing in rats: Persistence of high intakes of palatable solutions induced by 1-day-in-4 intermittent access.

When animals are given access to a palatable food or drink on some days but not on others, the amount they consume can far exceed the daily amounts consumed by controls given daily access. A previous study demonstrated such bingeing when rats were given 4% sucrose solution. Importantly, it also found that, following 1-day-in-4 access for many weeks, intakes remained persistently higher than that of controls even when the conditions were changed to 1-day-in-2 access for both groups. One aim of the three experiments reported here was to test whether such persistent bingeing could be found for other solutions. This was confirmed in rats for a saccharin solution and a highly palatable saccharin-plus-glucose solution. When a maltodextrin solution was used, the 1-day-in-4 schedule initially produced higher intakes than controls given daily access. However, the difference between these groups was not maintained when both were switched to a 1-day-in-2 schedule. These results suggest that the hedonic value of a solution is more important than its caloric content in determining whether it will support persistent bingeing. A second aim was to test for evidence that the 1-day-in-4 procedure induced an addiction to the target solution. No such evidence was found using multiple measures including instrumental responding and anxiety-like behavior on the elevated plus-maze for craving and withdrawal respectively.

Sodium saccharin can be more acceptable to rats than pure saccharin.

The artificial sweetener saccharin is available in several forms, including pure saccharin (S) and saccharin sodium salt hydrate (SSSH). Acceptance and preference relative to 2% sucrose for these two forms was assessed using both older female and young male rats. At the higher of two concentrations, ∼0.4%, SSSH was more acceptable and more greatly preferred over 2% sucrose than was a similar concentration of S, whereas little difference between the two forms was detected at the lower concentration, ∼0.1%. These results indicate the importance for researchers of care in choosing and reporting the form of saccharin they use.

A Meta-Analysis of the Effectiveness of Different Cortical Targets Used in Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Obsessive-Compulsive Disorder (OCD).

Randomised and sham-controlled trials (RCTs) of repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) have yielded conflicting results, which may be due to the variability in rTMS parameters used. We performed an updated systematic review and meta-analysis on the effectiveness of rTMS for the treatment of OCD and aimed to determine whether certain rTMS parameters, such as cortical target, may be associated with higher treatment effectiveness. After conducting a systematic literature review for RCTs on rTMS for OCD through to 1 December 2016 using MEDLINE, PubMed, Web of Science, PsycINFO, Google, and Google Scholar, we performed a random-effects meta-analysis with the outcome measure as pre-post changes in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To determine whether rTMS parameters may have influenced treatment effectiveness, studies were further analysed according to cortical target, stimulation frequency, and length of follow-up. Data were obtained from 18 RCTs on rTMS in the treatment of OCD. Overall, rTMS yielded a modest effect in reducing Y-BOCS scores with Hedge's g of 0.79 (95% CI = 0.43-1.15, p < 0.001). Stimulation of the supplementary motor area yielded the greatest reductions in Y-BOCS scores relative to other cortical targets. Subgroup analyses suggested that low frequency rTMS was more effective than high frequency rTMS. The effectiveness of rTMS was also greater at 12 weeks follow-up than at four weeks follow-up. Our meta-analysis implies that low frequency rTMS applied over the supplementary motor area may offer the greatest effectiveness in the treatment of OCD. The therapeutic effects of rTMS also appear to persist post-treatment and may offer beneficial long-term effectiveness. With our findings, it is suggested that future large-scale studies focus on the supplementary motor area and include follow-up periods of 12 weeks or more.

Metabolic and cognitive improvement from switching to saccharin or water following chronic consumption by female rats of 10% sucrose solution.

High consumption of sugar-sweetened beverages (SSBs) is a risk factor for weight gain and metabolic disease. Whether this risk is reduced by switching to 'diet' beverages containing low-calorie sweeteners (LCS) is controversial. Two experiments modeled whether a switch from SSB to LCS beverages produced positive outcomes on behavioral and metabolic measures. Both experiments consisted of a Stage 1, in which adult female rats received unrestricted access to 10% sucrose solution in addition to chow and water for 4 (Experiment 1) or 8 weeks (Experiment 2). In Stage 2 rats were switched to either saccharin (Suc-Sacch) or water (Suc-Water) or remained on 10% sucrose (Suc-Suc) for a further 4 (Experiment 1) or 7 weeks (Experiment 2). Experiment 2 contained a fourth group that was maintained on water throughout (Water-Water). In both experiments energy intake and weight gain in Stage 2 was reduced for Suc-Sacch and Suc-Water groups relative to the Suc-Suc groups and at cull the Suc-Suc groups showed poorer insulin sensitivity and greater g/kg fat than Suc-Water and Suc-Sacch groups. In Experiment 2 short-term place recognition memory was impaired at the end of Stage 1 but recovered to a similar extent in the Suc-Water and Suc-Sacch groups; when the latter groups were compared with the Water-Water group, recovery was found to be essentially complete. A higher saccharin concentration in Experiment 2 than in Experiment 1 increased absolute amounts of saccharin ingested but intake solution volumes remained low. These results show that switching from sucrose to either water or saccharin produces equivalent improvements on both metabolic and cognitive measures.

A library-screening approach for developing a fluorescence sensing array for the detection of metal ions.

Detection of individual metal ions is of importance across a range of fields of chemistry including environmental monitoring, and health and disease. Fluorescence is a highly sensitive technique and small fluorescent molecules are widely used for the detection and quantification of metal ions in various applications. Achieving specificity for a single metal from a single sensor is always a challenge. An alternative to selective sensing is the use of a number of non-specific sensors, in an array, which together respond in a unique pattern to each analyte. Here we show that screening a library of compounds can give a small sensor set that can be used to identify a range of metal ions following PCA and LDA. We explore a method for screening the initial compounds to identify the best performing sensors. We then present our method for reducing the size of the sensor array, resulting in a four-membered system, which is capable of identifying nine distinct metal ion species in lake water.