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Progress in Neuro-psychopharmacology &... Jul 2024Alcohol use disorder is a substantial social and economic burden. During the last years, the number of women with drinking problems has been increasing, and one main...
Alcohol use disorder is a substantial social and economic burden. During the last years, the number of women with drinking problems has been increasing, and one main concern is that they are particularly more vulnerable to negative consequences of alcohol. However, little is known about female-specific response patterns for alcohol, and potential underlying differences in brain mechanisms, including for compulsion-like alcohol drinking (when intake persists despite adverse consequences). We used lickometry to assess behavioral microstructure in adult Wistar male and female rats (n = 28-30) during alcohol-only drinking or moderate- or higher-challenge alcohol compulsion (10 or 60 mg/l quinine in alcohol, respectively). Estrous stages were determined and related to drinking levels and patterns of responding to alcohol, as was ovariectomy. Our findings showed that females (where we didn't determine estrus stage) had similar total licks in a session as males, but significantly longer licking bouts under alcohol-only and moderate-challenge, suggesting greater persistence. Further, greater intake under alcohol-only and moderate-challenge was related to faster licking in males, while female consumption was not related to licking speed. Thus, females could have increased persistence without greater vigor, unlike males. However, under higher-challenge, faster licking did predict higher intake in females, similar to males. To better understand female higher-challenge responding, we examined drinking in relation to phases of the estrous cycle. Higher-challenge had longer bouts only in late diestrus. In addition, ovariectomy led to longer bouts only under higher-challenge, suggesting that conditions with reduced hormone levels could increase female persistence for alcohol under higher-challenge. However, ovariectomy also reduced alcohol-only and moderate-challenge drinking but did not reduce bout length. Thus, intake level and response strategy could be regulated somewhat differently by ovarian hormones. Finally, moderate-challenge licking speed was less variable during early diestrus, and we previously showed more stereotyped responding specifically under moderate-challenge in males. By combining behavioral microstructure and sex- and estrus-related changes in drinking patterns, our results suggest that females have greater persistence for alcohol under lower-challenge drinking, while late diestrus and ovariectomy unmasked greater persistence under higher-challenge. Together, our novel insights could help develop more effective and personalized treatments for problematic alcohol use.
Topics: Animals; Female; Male; Rats; Rats, Wistar; Alcohol Drinking; Sex Characteristics; Ethanol; Ovariectomy; Estrous Cycle; Compulsive Behavior; Quinine
PubMed: 38641236
DOI: 10.1016/j.pnpbp.2024.111008 -
ELife Apr 2024Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly...
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC's recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (). Bengalese finch song includes several patterns: (1) comprising stereotyped syllable sequences; (2) , where a given syllable can be followed probabilistically by multiple syllables; and (3) , where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by 'breaks' in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.
Topics: Male; Animals; Songbirds; Speech; Acoustics; Memory; Stereotyped Behavior
PubMed: 38635312
DOI: 10.7554/eLife.93272 -
Methods in Molecular Biology (Clifton,... 2024Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited...
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.
Topics: Humans; Female; Pregnancy; Animals; Mice; Autism Spectrum Disorder; Prenatal Exposure Delayed Effects; Social Behavior; Cognitive Dysfunction; Models, Animal; Valproic Acid
PubMed: 38630242
DOI: 10.1007/978-1-0716-3810-1_28 -
Frontiers in Cellular Neuroscience 2024Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned and ingrained as habits, which can be evolutionarily... (Review)
Review
Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned and ingrained as habits, which can be evolutionarily advantageous as they reduce cognitive load and the expenditure of attentional resources. Repetitive behaviors can also be conscious and deliberate, and may occur in the absence of habit formation, typically when they are a feature of normal development in children, or neuropsychiatric disorders. They can be considered pathological when they interfere with social relationships and daily activities. For instance, people affected by obsessive-compulsive disorder, autism spectrum disorder, Huntington's disease and Gilles de la Tourette syndrome can display a wide range of symptoms like compulsive, stereotyped and ritualistic behaviors. The striatum nucleus of the basal ganglia is proposed to act as a master regulator of these repetitive behaviors through its circuit connections with sensorimotor, associative, and limbic areas of the cortex. However, the precise mechanisms within the striatum, detailing its compartmental organization, cellular specificity, and the intricacies of its downstream connections, remain an area of active research. In this review, we summarize evidence across multiple scales, including circuit-level, cellular, and molecular dimensions, to elucidate the striatal mechanisms underpinning repetitive behaviors and offer perspectives on the implicated disorders. We consider the close relationship between behavioral output and transcriptional changes, and thereby structural and circuit alterations, including those occurring through epigenetic processes.
PubMed: 38601025
DOI: 10.3389/fncel.2024.1386715 -
Cell Reports Apr 2024The insular cortex is involved in diverse processes, including bodily homeostasis, emotions, and cognition. However, we lack a comprehensive understanding of how it...
The insular cortex is involved in diverse processes, including bodily homeostasis, emotions, and cognition. However, we lack a comprehensive understanding of how it processes information at the level of neuronal populations. We leveraged recent advances in unsupervised machine learning to study insular cortex population activity patterns (i.e., neuronal manifold) in mice performing goal-directed behaviors. We find that the insular cortex activity manifold is remarkably consistent across different animals and under different motivational states. Activity dynamics within the neuronal manifold are highly stereotyped during rewarded trials, enabling robust prediction of single-trial outcomes across different mice and across various natural and artificial motivational states. Comparing goal-directed behavior with self-paced free consumption, we find that the stereotyped activity patterns reflect task-dependent goal-directed reward anticipation, and not licking, taste, or positive valence. These findings reveal a core computation in insular cortex that could explain its involvement in pathologies involving aberrant motivations.
Topics: Animals; Goals; Mice; Insular Cortex; Male; Motivation; Reward; Mice, Inbred C57BL; Neurons; Behavior, Animal; Cerebral Cortex
PubMed: 38568813
DOI: 10.1016/j.celrep.2024.114027 -
Journal of Neurophysiology May 2024The flexibility of the motor system to adjust a planned action before or during the execution of the movement in response to sensory information is critical for...
The flexibility of the motor system to adjust a planned action before or during the execution of the movement in response to sensory information is critical for preventing errors in motor control. As individuals age, this function declines, leading to an increased incidence of motor errors. Although sensory processing and cognitive decline are known contributors to this impairment, here, we test the hypothesis that repetition of context-specific planned actions interferes with the adjustment of feedforward motor commands. Younger and older participants were instructed to grasp and lift a T-shaped object with a concealed, off-sided center of mass and minimize its roll through anticipatory force control, relying predominantly on predictive model-driven planning (i.e., sensorimotor memories) developed through repeated lifts. We selectively manipulate the number of trial repeats with the center of mass on one side before switching it to the other side of the T-shaped object. The results showed that increasing the number of repetitions improved performance in manipulating an object with a given center of mass but led to increased errors when the object's center of mass was switched. This deleterious effect of repetition on feedforward motor adjustment was observed in younger and older adults. Critically, we show these effects on an internal model-driven motor planning task that relies predominantly on sensorimotor memory, with no differences in sensory inputs from the repetition manipulation. The findings indicate that feedforward motor adjustments are hampered by repetitive stereotyped planning and execution of motor behavior. Adjusting planned actions in response to sensory stimuli degrades with age contributing to increased incidence of errors ranging from clumsy spills to catastrophic falls. Multiple factors likely contribute to age-related motor inflexibility, including sensory- and cognition-supporting system declines. Here, we present compelling evidence for repetition to disrupt feedforward adjusting of motor commands in younger and older adults, which suggests increases in stereotypy as a deleterious potentiator of motor control errors.
Topics: Humans; Male; Aged; Female; Adult; Psychomotor Performance; Young Adult; Aging; Middle Aged; Hand Strength; Motor Activity
PubMed: 38568504
DOI: 10.1152/jn.00455.2023 -
American Journal of Primatology Jul 2024Gibbons (Hylobatidae) are the smallest of the apes, known for their arboreal behavior and stereotyped songs. These species and sex-specific songs are often the subject...
Gibbons (Hylobatidae) are the smallest of the apes, known for their arboreal behavior and stereotyped songs. These species and sex-specific songs are often the subject of detailed studies regarding their evolution, responses to changing environments, involvement in social behavior, and used to design vocalization-based survey techniques to monitor population densities and trends. What is poorly understood is the value and impact of using the science and sound of gibbon vocalization and gibbon stories in education and outreach to complement nongovernmental organizations (NGOs) efforts. We present an example of how Borneo Nature Foundation, a NGOs based in Indonesia, is working to use the recordings of the songs of Bornean white-bearded gibbons (Hylobates albibarbis) to inform conservation actions and education efforts. Gibbons in Indonesia are often poorly known or understood by the public compared to orangutans (Pongo spp). We showcase how a field of study, namely primate acoustics, is an untapped resource to create digital content to engage with local, national and international communities and can be developed into educational tools in the form of storytelling, mobile apps and games, to highlight the plight of these threatened species and how to conserve them.
Topics: Animals; Indonesia; Conservation of Natural Resources; Vocalization, Animal; Hylobates; Male; Female; Acoustics
PubMed: 38566320
DOI: 10.1002/ajp.23626 -
The International Journal of... May 2024The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard...
BACKGROUND
The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted.
METHODS
By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties.
RESULTS
2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs.
CONCLUSIONS
This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.
Topics: Animals; Male; Nucleus Accumbens; Dopamine; Serotonin; Prefrontal Cortex; Rats; Locomotion; Microdialysis; Age Factors; Behavior, Animal; Stereotyped Behavior; Vocalization, Animal; N-Methyl-3,4-methylenedioxyamphetamine; Rats, Wistar; Hallucinogens
PubMed: 38546531
DOI: 10.1093/ijnp/pyae016 -
Movement Disorders Clinical Practice Jun 2024This case series highlights the connection between childhood intense imagery movements (IIM) and adult-reported maladaptive daydreaming (MD). Motor stereotypies occur in... (Review)
Review
BACKGROUND
This case series highlights the connection between childhood intense imagery movements (IIM) and adult-reported maladaptive daydreaming (MD). Motor stereotypies occur in typically developing children and also with co-occurring neurodevelopmental differences. A subgroup with complex motor stereotypies reports accompanying intense imagery, often enhanced by the movements. This phenomenon can persist into adulthood and, in some cases, will need active management to prevent significant distress and impairment.
CASES
Six adults, self-reporting maladaptive daydreaming associated with stereotypies, are presented to demonstrate the associations.
LITERATURE REVIEW
The clinical significance and function of IIM and MD are unclear, but several hypotheses are discussed, including the mechanism of emotional regulation through sensory seeking, as a process for processing childhood psychological trauma, as intrusive thoughts or images as part of a subtype of Obsessive Compulsive Disorder, or as a result of diverse attentional networks seen in neurodevelopmental disorders.
CONCLUSIONS
This paper highlights important connections between IIM and MD. Many adults with MD show a childhood origin of stereotypical movements. Whilst immersive daydreaming may provide creativity and emotional regulation, there is evidence of distress and impairment of function for some adults, leading to MD diagnoses. Recognizing this phenomenon is important for all neurologists and physicians working with stereotypical movements.
Topics: Adult; Female; Humans; Male; Middle Aged; Fantasy; Imagination; Movement; Obsessive-Compulsive Disorder; Adolescent; Young Adult
PubMed: 38533626
DOI: 10.1002/mdc3.14011 -
Scientific Reports Mar 2024Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have...
Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.
Topics: Humans; Hydrocortisone; Autism Spectrum Disorder; Intellectual Disability; Stereotyped Behavior; Stereotypic Movement Disorder
PubMed: 38531943
DOI: 10.1038/s41598-024-57459-3