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Neuroscience Jun 2024The brown rat (Rattus norvegicus) is known to show three types of behavioral responses to novel objects. Whereas some rats are indifferent to novel objects, neophobic...
The brown rat (Rattus norvegicus) is known to show three types of behavioral responses to novel objects. Whereas some rats are indifferent to novel objects, neophobic and neophilic rats show avoidance and approach behavior, respectively. Here, we compared the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among these rats. Trapped wild rats and laboratory rats were first individually exposed to the novel objects in their home cage. Wild rats were divided into neophobic and indifferent rats depending on their behavioral responses. Similarly, laboratory rats were divided into neophilic and indifferent rats. Consistent with the behavioral differences, in the paraventricular nucleus of the hypothalamus, Fos expression in corticotropin-releasing hormone-containing neurons was higher in the neophobic rats than in the indifferent rats. In the anterior basal amygdala, the neophobic rats showed higher Fos expression than the indifferent rats. In the posterior basal amygdala, the neophobic and neophilic rats showed lower and higher Fos expressions than the indifferent rats, respectively. When we compared the neuromodulatory systems, in the dorsal raphe, the number of serotonergic neurons and Fos expression in serotonergic neurons increased linearly from neophobic to indifferent to neophilic rats. In the ventral tegmental area, Fos expression in dopaminergic neurons was higher in the neophilic rats than in the indifferent rats. These results demonstrate that approach/avoidance behavior to novel objects is correlated with the serotonergic and dopaminergic systems in the brown rat. We propose that the serotonergic system suppresses avoidance behavior while the dopaminergic system enhances approach behavior to novel objects.
Topics: Animals; Male; Rats; Avoidance Learning; Serotonergic Neurons; Dopaminergic Neurons; Dopamine; Serotonin; Proto-Oncogene Proteins c-fos; Brain; Exploratory Behavior; Behavior, Animal; Corticotropin-Releasing Hormone
PubMed: 38723837
DOI: 10.1016/j.neuroscience.2024.05.003 -
Neuroscience and Biobehavioral Reviews Jul 2024The mesopontine tegmentum, comprising the pedunculopontine tegmentum (PPN) and the laterodorsal tegmentum (LDT), is intricately connected to various regions of the basal... (Review)
Review
The mesopontine tegmentum, comprising the pedunculopontine tegmentum (PPN) and the laterodorsal tegmentum (LDT), is intricately connected to various regions of the basal ganglia, motor systems, and limbic systems. The PPN and LDT can regulate the activity of different brain regions of these target systems, and in this way are in a privileged position to modulate motivated behaviours. Despite recent findings, the PPN and LDT have been largely overlooked in discussions about the neural circuits associated with reward and aversion. This review aims to provide a timely and comprehensive resource on past and current research, highlighting the PPN and LDT's connectivity and influence on basal ganglia and limbic, and motor systems. Seminal studies, including lesion, pharmacological, and optogenetic/chemogenetic approaches, demonstrate their critical roles in modulating reward/aversive behaviours. The review emphasizes the need for further investigation into the associated cellular mechanisms, in order to clarify their role in behaviour and contribution for different neuropsychiatric disorders.
Topics: Reward; Humans; Animals; Tegmentum Mesencephali; Basal Ganglia; Avoidance Learning; Neural Pathways
PubMed: 38718986
DOI: 10.1016/j.neubiorev.2024.105702 -
Addiction Biology May 2024Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact...
Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.
Topics: Animals; Substance Withdrawal Syndrome; Reward; Motivation; Male; Goals; Morphine; Rats; Morphine Dependence; Narcotics; Conditioning, Operant
PubMed: 38706098
DOI: 10.1111/adb.13393 -
Scientific Reports May 2024Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently...
Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently reported that conditional deletion of Nrxn2, under the control of Emx1Cre promoter, predominately expressed in the neocortex and hippocampus (Emx1-Nrxn2 cKO mice) induced stereotyped patterns of behavior in mice, suggesting behavioral inflexibility. In this study, we investigated the effects of Nrxn2 deletion through two different conditional approaches targeting presynaptic cortical neurons projecting to dorsomedial striatum on the flexibility between goal-directed and habitual actions in response to devaluation of action-outcome (A-O) contingencies in an instrumental learning paradigm or upon reversal of A-O contingencies in a water T-maze paradigm. Nrxn2 deletion through both the conditional approaches induced an inability of mice to discriminate between goal-directed and habitual action strategies in their response to devaluation of A-O contingency. Emx1-Nrxn2 cKO mice exhibited reversal learning deficits, indicating their inability to adopt new action strategies. Overall, our studies showed that Nrxn2 deletion through two distinct conditional deletion approaches impaired flexibility in response to alterations in A-O contingencies. These investigations can lay the foundation for identification of novel genetic factors underlying behavioral inflexibility.
Topics: Animals; Mice; Mice, Knockout; Nerve Tissue Proteins; Behavior, Animal; Male; Neural Cell Adhesion Molecules; Gene Deletion; Maze Learning; Reversal Learning; Homeodomain Proteins; Hippocampus; Cell Adhesion Molecules, Neuronal; Conditioning, Operant; Transcription Factors
PubMed: 38702381
DOI: 10.1038/s41598-024-60760-w -
Scientific Reports May 2024Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity... (Randomized Controlled Trial)
Randomized Controlled Trial
Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.
Topics: Sleep Deprivation; Humans; Male; Female; Cross-Over Studies; Adult; Young Adult; Conditioning, Classical; Cues; Food; Feeding Behavior; Satiation; Conditioning, Operant; Appetitive Behavior
PubMed: 38693322
DOI: 10.1038/s41598-024-60223-2 -
Archives of Physical Medicine and... Apr 2024To examine the effect of an early postsurgical intervention consisting of graded activity and pain education (GAPE) in patients with chronic low back pain (CLBP)...
OBJECTIVES
To examine the effect of an early postsurgical intervention consisting of graded activity and pain education (GAPE) in patients with chronic low back pain (CLBP) undergoing lumbar spinal fusion (LSF) on sedentary behavior, disability, pain, fear of movement, self-efficacy for exercise and health-related quality of life (HRQoL) at 3-, 6-, and 12 months follow-up.
DESIGN
A parallel-group, observer-blinded randomized controlled trial.
SETTING
Department of Occupational- and Physiotherapy and the Centre for Rheumatology and Spine Diseases, Rigshospitalet, Denmark.
PARTICIPANTS
In total, 144 participants undergoing an LSF for CLBP were randomly assigned to an intervention or a control group.
INTERVENTIONS
The intervention group received 9 sessions of GAPE, based on principles of operant conditioning.
MAIN OUTCOME MEASURES
The primary outcome was reduction in time spent in sedentary behavior, measured by an accelerometer at 3 months. The secondary outcomes were reduction in time spent in sedentary behavior at 12 months and changes from baseline to 3-, 6-, and 12 months on disability, pain, fear of movement, self-efficacy for exercise, and HRQoL.
RESULTS
No difference in changes in sedentary behavior between groups was found 3 months after surgery. At 12 months after surgery, there was a significant difference between groups (mean difference: -25.4 min/d (95% confidence interval -49.1 to -1.7)) in favor of the intervention group.
CONCLUSIONS
Compared with usual care, GAPE had no effect on short-term changes in sedentary behavior but GAPE had a statistical, but possibly not clinical significant effect on sedentary behavior 12 months after LSF. Further, the behavioral intervention was safe to perform.
PubMed: 38685291
DOI: 10.1016/j.apmr.2024.04.005 -
Behaviour Research and Therapy Jul 2024Fibromyalgia is a chronic pain condition associated with substantial suffering and societal costs. Traditional cognitive behavior therapy (T-CBT) is the most evaluated... (Randomized Controlled Trial)
Randomized Controlled Trial
Fibromyalgia is a chronic pain condition associated with substantial suffering and societal costs. Traditional cognitive behavior therapy (T-CBT) is the most evaluated psychological treatment, but exposure therapy (Exp-CBT) has shown promise with a pronounced focus on the reduction of pain-related avoidance behaviors. In a recent randomized controlled trial (N = 274), we found that Exp-CBT was not superior to T-CBT (d = -0.10) in reducing overall fibromyalgia severity. This study investigated pain-related avoidance behaviors, pain catastrophizing, hypervigilance, pacing, overdoing and physical activity as potential mediators of the treatment effect. Mediation analyses were based on parallel process growth models fitted on 11 weekly measurement points, and week-by-week time-lagged effects were tested using random intercepts cross-lagged panel models. Results indicated that a reduction in avoidance behaviors, pain catastrophizing, and hypervigilance were significant mediators of change in both treatments. An increase in pacing and a reduction in overdoing were significant mediators in T-CBT only. Physical activity was not a mediator. In the time-lagged analyses, an unequivocal effect on subsequent fibromyalgia severity was seen of avoidance and catastrophizing in Exp-CBT, and of overdoing in T-CBT. Exposure-based and traditional CBT for fibromyalgia appear to share common treatment mediators, namely pain-related avoidance behavior, catastrophizing and hypervigilance.
Topics: Humans; Fibromyalgia; Female; Cognitive Behavioral Therapy; Implosive Therapy; Middle Aged; Catastrophization; Male; Adult; Treatment Outcome; Avoidance Learning; Anxiety
PubMed: 38685153
DOI: 10.1016/j.brat.2024.104546 -
Journal of Nutritional Science and... 2024Bitterness and astringency are the aversive tastes in mammals. In humans, aversion to bitterness and astringency may be reduced depending on the eating experience....
Bitterness and astringency are the aversive tastes in mammals. In humans, aversion to bitterness and astringency may be reduced depending on the eating experience. However, the cellular and molecular mechanisms underlying plasticity in preference to bitter and astringent tastants remain unknown. This study aimed to investigate the preference plasticity to bitter and astringent tea polyphenols, including catechins and tannic acids, in the model animal Caenorhabditis elegans. C. elegans showed avoidance behavior against epigallocatechin gallate (EGCG), tannic acid, and theaflavin. However, they displayed diminishing avoidance against EGCG depending on their EGCG-feeding regime at larval stages. Additionally, the behavioral plasticity in avoiding EGCG required the transcription factor DAF-16/FOXO. Isoform-specific deletion mutant analysis and cell-specific rescue analysis revealed that the function of daf-16 isoform b in AIY interneurons is necessary for experience-dependent behavioral plasticity to EGCG.
Topics: Animals; Catechin; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Forkhead Transcription Factors; Interneurons; Avoidance Learning; Biflavonoids; Taste; Tea; Behavior, Animal; Larva
PubMed: 38684387
DOI: 10.3177/jnsv.70.164 -
Journal of Integrative Neuroscience Apr 2024Much of the existing animal literature on the devaluation task suggests that prior repeated exposure to drugs of abuse during adulthood can impair goal-directed action,...
BACKGROUND
Much of the existing animal literature on the devaluation task suggests that prior repeated exposure to drugs of abuse during adulthood can impair goal-directed action, but the literature on human drug users is mixed. Also, the initiation of drug use often occurs during adolescence, but examinations of the effects of drug exposure during adolescence on behavior in the devaluation task are lacking.
METHODS
We examined whether repeated exposure during adolescence to amphetamine (3 mg/kg injections every-other day from post-natal day 27-45) or ketamine (twice daily 30 mg/kg injections from post-natal day 35-44) would impair behavior in a devaluation test when tested drug-free in adulthood. Rats were trained to press a left lever with a steady cue-light above it for one reinforcer and a right lever with a flashing cue-light above it for a different reinforcer. We tested whether any impairments in goal-directed action could be overcome by compensation between strategies by giving rats information based on lever-location and cue-lights during the test that was either congruent (allowing compensation) or incongruent (preventing compensation between strategies) with the configurations during training.
RESULTS
Our results provided no evidence for impairment of goal-directed action during adulthood after adolescent amphetamine or ketamine exposure.
CONCLUSIONS
We discuss possible reasons for this discrepancy with the prior literature, including (1) the age of exposure and (2) the pattern in the previous literature that most previous demonstrations of drug exposure impairing devaluation in laboratory animals may be attributed to either drug-associated cues present in the testing environment and/or accelerated habit learning in tasks that predispose laboratory animals towards habit formation with extended training (with training procedures that should resist the formation of habits in the current experiment). However, additional research is needed to examine the effects of these factors, as well a potential role for the particular doses and washout periods to determine the cause of our finding of no devaluation impairment after drug exposure.
Topics: Animals; Ketamine; Amphetamine; Male; Rats; Conditioning, Operant; Central Nervous System Stimulants; Rats, Long-Evans; Behavior, Animal; Age Factors; Cues
PubMed: 38682231
DOI: 10.31083/j.jin2304083 -
Journal of Integrative Neuroscience Apr 2024Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily...
BACKGROUND
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety.
METHODS
This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation.
RESULTS
No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze.
CONCLUSIONS
These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.
Topics: Subthalamic Nucleus; Deep Brain Stimulation; Animals; Oxidopamine; Male; Disease Models, Animal; Behavior, Animal; Parkinsonian Disorders; Anxiety; Rats; Rats, Sprague-Dawley; Avoidance Learning; Parkinson Disease
PubMed: 38682230
DOI: 10.31083/j.jin2304084