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Rationale Female rodents consume more ethanol (EtOH) than males and exhibit greater aversion-resistant drinking in some paradigms. Ovarian hormones promote EtOH drinking but the contribution of ovarian hormones to aversion-resistant drinking has not been assessed. Objectives We aimed to investigate the role of ovarian hormones to aversion-resistant drinking in female mice in a drinking in the dark (DID) task. Methods Female C57BL/6 J mice first underwent an ovariectomy (OVX, n = 16) or sham (SHAM, n = 16) surgery. Four weeks following surgery, mice underwent a DID paradigm where they were given access to water and 15% EtOH 3 h into the dark cycle for up to 4 h across 15 drinking sessions. To assess frontloading behavior, bottles were weighed at 30 min, 2 h, and 4 h. Aversion-resistance was tested by adding escalating concentrations of quinine (0, 100, 250, and 500 µM) to the 15% EtOH bottle on sessions 16 – 19. Results Removal of the ovaries reduced EtOH consumption in OVX subjects. When assessing aversion-resistant EtOH drinking, mice with ovarian hormones (SHAM) reduced consumption of 250 and 500 µM quinine in EtOH, while OVX subjects exhibited aversion-resistance at all quinine concentrations. OVX mice had greater frontloading for quinine + EtOH at higher concentrations of quinine. Conclusions These results indicate that circulating ovarian hormones may be protective against the development of aversion-resistant EtOH drinking and call for further investigation of the role of ovarian hormones in models of addictive behavior.

Conflict between humans and black bears ( Ursus americanus ) occurs throughout North America with increasing public demand to replace lethal management with non-lethal methods, such as aversive conditioning (AC). AC aims to teach animals to associate negative stimuli with humans or their infrastructure. We sought to test the efficacy of AC using radio-collared black bears in Whistler, British Columbia, by monitoring individuals and assigning those in conflict with people to control or treatment groups. We measured wariness using overt reaction distance, displacement distance, and reaction to researchers before, during and after executing 3–5-day AC programs that consisted of launching projectiles at bears in the treatment group. We also assessed predictors of successful AC events (i.e., leaving at a run), changes in bear use of human-dominated habitat during the day and at night, and the effects of including a sound stimulus to signal the beginning and end of AC events. Among treated bears, overt reaction distance increased by 46.5% and displacement distance increased by 69.0% following AC programs, whereas both overt reaction distance and displacement distance decreased over time among control group bears. Each additional AC event during the previous 30 days increased likelihood of bear departure in response to researcher presence by 4.5%. The success of AC events varied among individuals, declined with distance to cover, and increased with exposure to previous AC events. Projectiles launched from guns were slightly more effective at causing bears to displace compared to those launched from slingshots, and sound stimuli decreased the likelihood of a successful AC event. AC did not alter diurnal use by bears of human-dominated habitat. Our results suggest that AC effectively increases short-term wariness in black bears but does not alter bear use of human-dominated spaces, highlighting the importance of proactive attractant management and prevention of food conditioning.

Alcohol dependence (AD) is characterized by a high relapse rate. Virtual reality (VR) technology can provide immersive cue exposure therapy (VR‐CET) and aversion therapy (VR‐AT). This study aimed to evaluate the efficacy of VR‐CET, VR‐AT and their combination on craving, emotional and sleep states, attentional bias and relapse rate in patients with AD. In this single‐centre randomized controlled trial, male inpatients with AD were randomly assigned to one of four groups: control, VR‐CET, VR‐AT or combined VR‐CET + AT (target n = 25 per group; 80 completed, 20 per group). The interventions spanned 15 days with eight sessions (VR‐CET + AT 20 min/session; others 10 min). Assessments were conducted before and after treatment using the Visual Analogue Scale (VAS), the Pennsylvania Alcohol Craving Scale (PACS), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Pittsburgh Sleep Quality Index (PSQI). Eye‐tracking and grasping indices in VR environments were used to assess attentional bias (e.g., alcohol‐cue fixation time ratio). Relapse was evaluated by telephone at 4 and 12 weeks post‐treatment. Statistical analyses used Shapiro–Wilk tests and ANOVA/Kruskal–Wallis tests with appropriate post hoc comparisons (α = 0.05). All groups showed significant pre‐ to post‐treatment improvements in PACS, HAMD, HAMA, PSQI and VAS scores (all p < 0.001). Between‐group comparisons at post‐treatment revealed significant differences in alcohol‐cue fixation time ratio (p < 0.05), with the VR‐CET + AT group showing a lower fixation time ratio than the control group. VAS scores also differed among groups (p < 0.05), with the control group showing higher values than the VR‐CET + AT group. Changes in alcohol‐cue fixation time ratio from pre‐ to post‐treatment were significantly greater in the VR‐CET + AT group than in the control group. Relapse rates at 4 and 12 weeks (47/80 reached by telephone follow‐up) did not significantly differ among groups (both p > 0.05). Combining VR‐CET with VR‐AT reduced craving (VAS) and attentional bias (alcohol‐cue fixation time ratio) beyond standard care, whereas all groups improved on clinical scales. Larger and longer trials are warranted to further clarify relapse outcomes. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500110026. Registered 29 September 2025 (retrospectively registered) Virtual reality–based cue exposure therapy and aversion therapy were evaluated in male inpatients with alcohol dependence. The combined VR‐CET+AT intervention reduced craving and alcohol‐related attentional bias beyond standard care, whereas relapse rates did not differ significantly at 4 or 12 weeks. These findings support VR‐based interventions as promising adjunctive approaches for alcohol dependence.

IntroductionAnthony Burgess’ novel ‘Clockwork Orange’ identifies the topical debates surrounding the use of aversion therapy (or aversive conditioning) as an effective treatment for addictive behaviours. Widely popularised in literature as ‘Ludovico’s Technique’, Burgess attempts to credit the misunderstanding and dramatization of its effects when the main protagonist is released from a prison sentence after undergoing this treatment.ObjectivesWe aimed to highlight the depictions of aversion therapy in modern popular literature.MethodsA narrative review of the current literature concerning aversion therapy and Anthony Burgess’s novel ‘A Clockwork Orange’ was conducted. Emphasis on the misinterpretation of aversive therapies was noted.ResultsSince the introduction of pharmacological alternatives and additional forms of psychological therapies, there has been a decline in the use of aversion therapy in recent decades. However, it is still effective when conceding the conditioning process. Likewise, its predecessor’ visual imagery’ is believed to be a more acceptable and effective form.ConclusionsThe depiction of aversion therapy in literature and media has played a role in shaping societal views on aversive conditioning techniques and the degree to which they are deemed acceptable forms of treatment. The “Ludovico Technique” featured in the novel ‘A Clockwork Orange’ and its film adaptation is arguably the most salient depiction of aversion therapy in popular culture.DisclosureNo significant relationships.

Reducing psychological craving is critical for preventing relapse in methamphetamine use disorder (MUD). This study aimed to evaluate the efficacy of virtual reality (VR)-based cue exposure therapy (CET) and cue exposure with aversion therapy (CETA) in reducing methamphetamine craving in men with MUD. In this randomized controlled trial, 89 men with MUD were assigned to three groups: VR-based cue exposure therapy (CET, n  = 30), VR-based cue exposure combined with aversion therapy (CETA, n  = 29), and neutral scenes (NS, n  = 30). The intervention comprised 16 sessions over 8 weeks. Primary outcomes were tonic craving and cue-induced craving. Secondary outcomes included attentional bias, rehabilitation confidence, drug refusal self-efficacy, anxiety, and depression. Both CET and CETA groups demonstrated significant reductions in tonic craving post-intervention (CET: p  = 0.001; CETA: p  = 0.010), while the NS group showed no change ( p  = 0.217). The CET group demonstrated significantly lower post-intervention tonic craving compared to the NS group ( p  = 0.047). All groups showed decreased cue-induced craving in drug use scenes ( p  < 0.05). The CETA group showed significantly improved drug refusal self-efficacy compared to baseline ( p  = 0.001) and the NS group ( p  = 0.018). The CET group demonstrated reduced anxiety compared to the NS group ( p  = 0.014). No serious adverse events were reported during VR exposure. VR-based cue exposure therapy, particularly when combined with aversion therapy, effectively reduces psychological craving and improves drug refusal self-efficacy in MUD patients. This study provides evidence supporting VR-based interventions as a safe and promising tool for MUD treatment, though larger-scale trials are needed to confirm long-term efficacy. Clinical trial number : This randomized controlled trial was registered with the Chinese Clinical Trial Registry (Code: ChiCTR1800020014).

Honey bees, Apis mellifera, are a globally significant pollinator species and are currently in decline, with losses attributed to an array of interacting environmental stressors. Extremely low frequency electromagnetic fields (ELF EMFs) are a lesser-known abiotic environmental factor that are emitted from a variety of anthropogenic sources, including power lines, and have recently been shown to have a significant impact on the cognitive abilities and behaviour of honey bees. Here we have investigated the effects of field-realistic levels of ELF EMFs on aversive learning and aggression levels, which are critical factors for bees to maintain colony strength. Bees were exposed for 17 h to 100 μT or 1000 μT ELF EMFs, or a sham control. A sting extension response (SER) assay was conducted to determine the effects of ELF EMFs on aversive learning, while an intruder assay was conducted to determine the effects of ELF EMFs on aggression levels. Exposure to both 100 μT and 1000 μT ELF EMF reduced aversive learning performance by over 20%. Exposure to 100 μT ELF EMFs also increased aggression scores by 60%, in response to intruder bees from foreign hives. These results indicate that short-term exposure to ELF EMFs, at levels that could be encountered in bee hives placed under power lines, reduced aversive learning and increased aggression levels. These behavioural changes could have wider ecological implications in terms of the ability of bees to interact with, and respond appropriately to, threats and negative environmental stimuli.

Objective This study aims to evaluate the effectiveness of virtual reality‐based aversion therapy in reducing craving, alleviating depression, and improving self‐efficacy in patients with substance use disorders undergoing methadone maintenance therapy. Methods The research was conducted as an interventional clinical trial involving 90 participants aged 25 to 55 years from outpatient treatment centers. The participants were randomly assigned to one of three groups: a group that received virtual reality‐based aversion therapy combined with methadone, a group that received psychological counseling combined with methadone, and a group that received methadone only. Results The findings revealed significant differences between the groups' means for depression (F = 19.652, p = 0.000), self‐efficacy (F = 33.956, p = 0.000), and craving (F = 65.445, p = 0.000 for desire and intent to use substances; F = 45.931, p = 0.000 for craving and negative reinforcement; F = 76.202, p = 0.000 for pleasure and intensity of lack of control). Specifically, virtual reality‐based aversion therapy significantly reduced the desire and intent to use substances, craving and negative reinforcement, and pleasure and intensity of lack of control compared to both psychological counseling and control groups. It also significantly reduced depression and enhanced self‐efficacy compared to both psychological counseling and control groups. This therapy, implemented through Python programming in a virtual reality environment with interactive and controlled simulations, facilitated gradual exposure to negative stimuli, cognitive restructuring, and the reinforcement of positive behaviors. Conclusion The results underscore the high potential of virtual reality–based aversion therapy to improve the effectiveness and quality of substance abuse treatment. This study emphasizes the necessity of further research in this field to improve therapeutic interventions and presents virtual reality‐based aversion therapy as an innovative, complementary, or alternative approach to substance use treatment. This study demonstrated that VR‐based aversion therapy combined with methadone treatment significantly reduced cravings, depression, and the desire to use substances while enhancing self‐efficacy

RationaleThe nature and predictors of insensitivity to aversive consequences of heroin + cocaine polysubstance use are not well characterized.ObjectivesTranslational methods incorporating a tightly controlled animal model of drug self-administration and measures of inhibitory control and avoidance behavior might be helpful for clarifying this issue.MethodsThe key approach for distinguishing potential contributions of pre-existing inhibitory control deficits vs. drug use history in meditating insensitivity to aversive consequences was comparison of two rat strains: Wistar (WIS/Crl), an outbred strain, and the spontaneously hypertensive rat (SHR/NCrl), an inbred strain shown previously to exhibit heightened cocaine and heroin self-administration and poor inhibitory control relative to WIS/Crl.ResultsIn separate tasks, SHR/NCrl displayed greater impulsive action and compulsive-like behavior than WIS/Crl prior to drug exposure. Under two different schedules of drug delivery, SHR/NCrl self-administered more cocaine than WIS/Crl, but self-administered a similar amount of heroin + cocaine as WIS/Crl. When half the session cycles were punished by random foot shock, SHR/NCrl initially were less sensitive to punishment than WIS/Crl when self-administering cocaine, but were similarly insensitive to punishment when self-administering heroin + cocaine. Based on correlation analyses, only trait impulsivity predicted avoidance capacity in rats self-administering cocaine and receiving yoked-saline. In contrast, only amount of drug use predicted avoidance capacity in rats self-administering heroin + cocaine. Additionally, baseline drug seeking and taking predicted punishment insensitivity in rats self-administering cocaine or heroin + cocaine.ConclusionsBased on the findings revealed in this animal model, human laboratory research concerning the nature and predictors of insensitivity to aversive consequences in heroin and cocaine polysubstance vs. monosubstance users is warranted.

RationaleRecovery from a traumatic experience requires extinction of cue-based fear responses, a process that is impaired in post-traumatic stress disorder. While studies suggest a link between fear behavioral flexibility and noradrenaline signaling, the role of specific receptors and brain regions in these effects is unclear.ObjectivesHere, we examine the role of prazosin, an α1-adrenergic receptor (α1-AR) antagonist, in auditory fear conditioning and extinction.MethodsC57Bl/6N mice were subjected to auditory fear conditioning and extinction in combination with systemic (0.1–2 mg/kg) or local microinjections (3 or 6 mM) of the α1-AR antagonist prazosin into the prelimbic division of medial prefrontal cortex or basolateral amygdala. Conditioned fear and anxiety-like behaviors were compared with vehicle-injected control animals.ResultsMice that received systemic prazosin prior to fear conditioning exhibited similar initial levels of cue-elicited freezing compared to vehicle controls on the following day. However, at all doses tested, fear that was acquired during prazosin treatment was more readily extinguished, whereas anxiety-like behavior on the day of extinction was unaffected. A similar pattern of results was observed when prazosin was microinjected into the basolateral amygdala but not the prelimbic cortex. In contrast to pre-conditioning injections, prazosin administration prior to extinction had no effect on freezing.ConclusionsOur results indicate that α1-AR activity during aversive conditioning is dispensable for memory acquisition but renders conditioned fear more impervious to extinction. This suggests that behavioral flexibility is constrained by noradrenaline at the time of initial learning via activation of a specific AR isoform.