70 research outputs found

    Maintenance of aversive memories shown by fear extinction-impaired phenotypes is associated with increased activity in the amygdaloid-prefrontal circuit

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    Although aversive memory has been mainly addressed by analysing the changes occurring in average populations, the study of neuronal mechanisms of outliers allows understanding the involvement of individual differences in fear conditioning and extinction. We recently developed an innovative experimental model of individual differences in approach and avoidance behaviors, classifying the mice as Approaching, Balancing or Avoiding animals according to their responses to conflicting stimuli. The approach and avoidance behaviors appear to be the primary reactions to rewarding and threatening stimuli and may represent predictors of vulnerability (or resilience) to fear. We submitted the three mice phenotypes to Contextual Fear Conditioning. In comparison to Balancing animals, Approaching and Avoiding mice exhibited no middle- or long-term fear extinction. The two non-extinguishing phenotypes exhibited potentiated glutamatergic neurotransmission (spontaneous excitatory postsynaptic currents/spinogenesis) of pyramidal neurons of medial prefrontal cortex and basolateral amygdala. Basing on the a priori individuation of outliers, we demonstrated that the maintenance of aversive memories is linked to increased spinogenesis and excitatory signaling in the amygdala-prefrontal cortex fear matri

    Dissecting the neuronal basis of threat responding in mice

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    Environmental threats demand adaptive defensive responses of an organism that ensure its survival. Extreme stressors, however, can unbalance stress homeostasis and lead to long-term changes that impair appropriate defensive behaviors and emotional responses. In my thesis, I assessed (1) the interaction of two stress-related neuromodulatory systems, (2) the effects of a traumatic incident on brain volume and hyperarousal, and (3) sonic vocalization as a defensive behavior in mice, and discussed the topics in three independent studies.In the first study, I evaluated the interaction of two regulatory systems with respect to fear, anxiety, and trauma-related behaviors. Although the endocannabinoid and the corticotropin-releasing factor (CRF) systems are well described in modulating stressrelatedresponses, the direct interaction of both systems remained poorly understood. The generation of a new conditional knockout mouse line that selectively lacked the expression of the cannabinoid type 1 (CB1) receptor in CRF-positive neurons presented no differences in various tests of fear and anxiety-related behaviors under basal conditions or after a traumatic event. Also stress hormone levels were unaffected. However, male knockout animals exhibited a significantly increased acoustic startle response thus suggesting a specific involvement of CB1-CRF interactions in controlling arousal.In the second study, I assessed the consequences of a traumatic experience on behavior and grey matter volume in mice. Whole-brain deformation-based morphometry (DBM) by means of magnetic resonance imaging (MRI) after incubation of a traumatic incident showed changes in the dorsal hippocampus and the reticular nucleus. Using the severity of hyperarousal as regressor for cross-sectional volumetric differences between traumatized mice and controls revealed a negative correlation with the dorsal hippocampus. Further, longitudinal analysis including volumetric measurements before and after the traumatic incident showed that volume reductions in the globus pallidus reflect trauma-related changes in hyperarousal severity.In the third study, I characterized sonic vocalization as a defensive behavior in mice. Mice bred for high anxiety-related behavior (HAB) were found to have a high disposition to emit audible squeaks when taken by the tail which was not the case for any of the other five mouse lines tested. The calls emitted had a fundamental frequency of 3.8 kHz and were shown to be sensitive to anxiolytic but not panicolytic compounds. Manganese-enhanced MRI (MEMRI) scans pointed towards an increased tonic activity, among others, in the periaqueductal grey (PAG). Inhibition of the dorsal PAG by muscimol not only completely abolished sonic vocalization, but also reduced anxiety-like behavior. This suggests that sonic vocalization of mice is related to anxiety and controlled by the PAG. To explore the ecological relevance of defensive vocalization, I performed playback experiments with conspecifics and putative predators. Squeaks turned out to be aversive to HAB mice but became appetitive to both mice and rats when a stimulus mouse was present during playback.Collectively, the results of this thesis provide novel insights into fear and anxiety-related behaviors and shine light onto their mechanistic basis and ecological relevance

    Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

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    The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding

    Addictions

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    Addiction, increasingly perceived as a heterogeneous brain disorder, is one of the most peculiar psychiatric pathologies in that its management involves various, often non-overlapping, resources from the biological, psychological, medical, economical, social, and legal realms. Despite extensive efforts from the players of these various fields, to date there are no reliably effective treatments of addiction. This may stem from a lack of understanding of the etiology and pathophysiology of this disorder as well as from the lack of interest into the potential differences among patients in the way they interact compulsively with their drug. This book offers an overview of the psychobiology of addiction and its current management strategies from pharmacological, social, behavioural, and psychiatric points of view

    CBD

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    A comprehensive review of the scientific literature on the possible benefits of CBD, describing findings from both preclinical and human clinical studies. CBD (cannabidiol), a nonintoxicating compound derived from the cannabis plant, can be found in products ranging from lotion and smoothies to chewable gummies and pet treats. It's been promoted—but not always scientifically validated—as a treatment for medical conditions including psychosis, anxiety, pain, and even cancer. In this book, three leading cannabis researchers look at the science of CBD, offering a comprehensive review of the scientific literature on the possible benefits of CBD and describing their findings from both preclinical and human clinical studies. As it turns out, the current CBD fad has some basis in preclinical animal research that indicates potential beneficial effects. Clinical studies, hampered by regulations governing research with cannabis, have lagged behind the basic animal research. The authors examine what research shows about chemical and pharmacological aspects of CBD and CBD's interaction with THC, the main psychotropic compound found in cannabis. They go on to review the current state of knowledge about CBD's effectiveness in treating epilepsy, cancer, nausea, pain, anxiety, PTSD, depression, sleep disorders, psychosis, and addiction

    MODERATE FETAL ALCOHOL EXPOSURE, THE NUCLEUS ACCUMBENS, AND ALCOHOL CONSUMPTION IN ADULTHOOD

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    Recent findings using a moderate prenatal alcohol consumption model in rats found that male offspring had reduced dendritic fields in medium spiny neurons of the nucleus accumbens (NAc). These results suggest that moderate fetal alcohol exposure (FAE) leads to long-lasting alterations in brain regions involved in reward processing that could lead to abnormal behavior related to ethanol (EtOH) in adulthood. Here, five experiments were carried out to establish the extent to which moderate FAE leads to increased EtOH consumption in adulthood, how functional and structural alterations in the NAc are related to EtOH consumption, and whether moderate FAE has any effect on EtOH metabolism and general reward learning. Rats exposed to moderate FAE had increased consumption and preference for both a 10% and 20% EtOH solution across several weeks of exposure, and FAE animals also had significant reductions in measures of NAc core and shell dendritic morphology, as well as reductions in core Homer1a immediate-early gene expression. In control animals, measures of shell dendritic morphology and core Arc expression served as significant predictors of ethanol consumption while core dendritic morphology predicted EtOH consumption in FAE rats. No significant differences were found between FAE animals and controls for measures of general reward processing in an intra cranial self-stimulation task or for EtOH metabolism. These results suggest that moderate FAE results in structural and functional alterations in the NAc, and that these effects have important implications for reward processing and EtOH consumption in adulthood
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