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The International Journal of... May 2017Previous studies suggested that opiate withdrawal may increase anxiety and disrupt brain-derived neurotrophic factor function, but the effects of i.v. morphine...
BACKGROUND
Previous studies suggested that opiate withdrawal may increase anxiety and disrupt brain-derived neurotrophic factor function, but the effects of i.v. morphine self-administration on these measures remain unclear.
METHODS
Adult male Sprague-Dawley rats were implanted with a catheter in the jugular vein. After 1 week of recovery, the animals were allowed to self-administer either i.v. morphine (0.5 mg/kg per infusion, 4 h/d) or saline in the operant conditioning chambers. The acoustic startle reflex and prepulse inhibition were measured at a baseline and on self-administration days 1, 3, 5, and 7 (1- and 3-hour withdrawal). Blood samples were collected on self-administration days 3, 5, and 7 from separate cohorts of animals, and the levels of brain-derived neurotrophic factor and corticosterone were assayed using the enzyme-linked immunosorbent assay method.
RESULTS
Compared with the saline group, the morphine self-administration group showed hyper-locomotor activity and reduced defecation during the self-administration. The morphine self-administration increased acoustic startle reflex at 1-hour but not 3-hour withdrawal from morphine and disrupted prepulse inhibition at 3-hour but not 1-hour withdrawal. The blood brain-derived neurotrophic factor levels were decreased in the morphine self-administration group at self-administration days 3 and 5, while the corticosterone levels remained unchanged throughout the study.
CONCLUSIONS
The current findings suggest that spontaneous withdrawal from i.v. morphine self-administration may have transient effects on acoustic startle, sensorimotor gating, and peripheral brain-derived neurotrophic factor levels, and these changes may contribute to the adverse effects of opiate withdrawal.
Topics: Acoustic Stimulation; Analgesics, Opioid; Analysis of Variance; Animals; Brain-Derived Neurotrophic Factor; Conditioning, Operant; Enzyme-Linked Immunosorbent Assay; Hydrocortisone; Male; Morphine; Prepulse Inhibition; Rats; Rats, Sprague-Dawley; Reflex, Startle; Self Administration; Time Factors
PubMed: 27927738
DOI: 10.1093/ijnp/pyw107 -
Psychological Science Jul 2019In classical fear conditioning, neutral conditioned stimuli that have been paired with aversive physical unconditioned stimuli eventually trigger fear responses. Here,...
In classical fear conditioning, neutral conditioned stimuli that have been paired with aversive physical unconditioned stimuli eventually trigger fear responses. Here, we tested whether aversive mental images systematically paired with a conditioned stimulus also cause de novo fear learning in the absence of any external aversive stimulation. In two experiments ( = 45 and = 41), participants were first trained to produce aversive, neutral, or no imagery in response to three different visual-imagery cues. In a subsequent imagery-based differential-conditioning paradigm, each of the three cues systematically coterminated with one of three different neutral faces. Although the face that was paired with the aversive-imagery cue was never paired with aversive external stimuli or threat-related instructions, participants rated it as more arousing, unpleasant, and threatening and displayed relative fear bradycardia and fear-potentiated startle. These results could be relevant for the development of fear and related disorders without trauma.
Topics: Adult; Conditioning, Classical; Cues; Emotions; Facial Expression; Fear; Female; Humans; Imagination; Male; Reflex, Startle; Young Adult
PubMed: 31150589
DOI: 10.1177/0956797619842261 -
Hearing Research Apr 2019Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at... (Review)
Review
Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.
Topics: Acoustic Stimulation; Animals; Auditory Cortex; Auditory Pathways; Bridged Bicyclo Compounds; Cochlea; Evoked Potentials, Auditory, Brain Stem; Excitatory Amino Acid Agonists; Humans; Inhibitory Postsynaptic Potentials; Mice; Prepulse Inhibition; Psychoacoustics; Receptors, Metabotropic Glutamate; Reflex, Startle; Tinnitus
PubMed: 30822633
DOI: 10.1016/j.heares.2019.01.022 -
Alcoholism, Clinical and Experimental... Oct 2018Researchers have long sought to understand how individuals respond to alcohol in social settings with the aim of elucidating pathways of risk for alcohol use disorder...
BACKGROUND
Researchers have long sought to understand how individuals respond to alcohol in social settings with the aim of elucidating pathways of risk for alcohol use disorder (AUD). But studies that incorporate a social context are still outnumbered by those that examine alcohol's subjective effects among participants drinking alcohol in isolation. Further, perhaps due to the challenges of capturing automatic affective processes in these settings, prior studies of alcohol response in social context have relied mainly on self-report measures, and so relatively little is known about alcohol's psychophysiological effects in social settings.
METHODS
Using a novel paradigm that integrated alcohol-administration procedures, startle methodology, and social context, this study examined the impact of alcohol and social context on startle eyeblink reflex among 40 social drinkers.
RESULTS
Results indicated that there was a significant effect of group presence, indicating that startle magnitude was larger when people were alone than with others. There was a significant group presence-by-alcoholic beverage interaction, with the effect of alcohol being significantly larger when people were alone versus with others. These effects were found both for the startle habituation data and during the picture-viewing task.
CONCLUSIONS
Results of this study highlight the importance of considering the presence of other individuals for understanding alcohol response and mechanisms of AUD risk. Findings are discussed in light of both emotional and cognitive correlates of startle reflex magnitude. Future research should examine these effects within larger samples of participants and further explore mechanisms that might underlie these effects.
Topics: Adult; Alcohol Drinking; Blinking; Female; Humans; Male; Photic Stimulation; Reflex, Startle; Social Environment; Young Adult
PubMed: 29989675
DOI: 10.1111/acer.13838 -
Medicina (Kaunas, Lithuania) Sep 2023: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations....
: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. : After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. : We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. : In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.
Topics: Animals; Tinnitus; Reflex, Startle; Deafness; Anxiety; Anxiety Disorders
PubMed: 37763802
DOI: 10.3390/medicina59091683 -
Revista de Neurologia Dec 2017Prepulse inhibition (PPI) of the startle response is an index used to evaluate how the pre-attention system works. PPI is altered in patients with a mental disorder such... (Review)
Review
INTRODUCTION
Prepulse inhibition (PPI) of the startle response is an index used to evaluate how the pre-attention system works. PPI is altered in patients with a mental disorder such as schizophrenia and in subjects who are vulnerable to it. Likewise, cocaine users also frequently exhibit psychiatric disorders as schizophrenia.
AIM
To know the alterations that cocaine produces on PPI.
DEVELOPMENT
A comprehensive review is carried out, covering both clinical and preclinical studies with animal models that have evaluated the effects of cocaine exposure on the PPI paradigm. Underlying neural bases and mechanisms of action are suggested to explain these findings.
CONCLUSIONS
Cocaine alters PPI through its action on the dopaminergic system. Acute exposure of cocaine decreases PPI by increasing dopamine, while with chronic use, depending on withdrawal time, PPI can be restored. However, the effects of cocaine on PPI appear to depend on the baseline levels of PPI shown by the individual. Thus, since a deficit in PPI has been associated with a greater vulnerability to developing mental pathologies such as schizophrenia, PPI level in subjects could be considered as a biomarker of psychiatric vulnerability. Therefore, a better understanding of the effect of drugs such as cocaine on PPI may help to understand the development of dual pathology.
Topics: Cocaine; Humans; Prepulse Inhibition; Reflex, Startle
PubMed: 29178109
DOI: No ID Found -
Scientific Reports Aug 2023Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity... (Randomized Controlled Trial)
Randomized Controlled Trial
Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.
Topics: Male; Humans; Reflex, Startle; Cross-Over Studies; Ketamine; Brain; Emotions
PubMed: 37587171
DOI: 10.1038/s41598-023-40099-4 -
Scientific Reports Nov 2022Repeat-associated non-AUG translation (RAN translation) is observed in transcripts that are causative for polyglutamine (polyQ) diseases and generates proteins with mono...
Repeat-associated non-AUG translation (RAN translation) is observed in transcripts that are causative for polyglutamine (polyQ) diseases and generates proteins with mono amino acid tracts such as polyalanine (polyA), polyleucine (polyL) and polyserine (polyS) in neurons, astrocytes and microglia. We have previously shown that microglia with aggregated polyQ led to defective differentiation and degeneration of neuron-like cells. However, it has not been determined whether only microglia containing a specific RAN product, but not other RAN products, is harmful in vitro and in vivo. Here we show that polyL-incorporating microglia specifically led to altered startle response in mice. Aggregated polyA, polyS and polyL induced aberrant differentiation of microglia-like BV2 cells. Differentiated PC12 cells treated with conditioned medium (CM) of polyS- and polyL- but not polyA-incorporating microglia-like BV2 cells showed retraction of neurites and loss of branch of neurites. Injection of the polyL-CM, but not polyA-CM and polyS-CM, into the lateral ventricle lowered startle response in mice. Consistently, polyL induced the highest expression of CD68 in BV2 cells. The lowered startle response was replicated in mice given the polyL-CM in the caudal pontine reticular nucleus (PnC), the key region of startle response. Thus, endogenous RAN proteins having polyL derived from polyQ diseases-causative genes in microglia might specifically impair startle response.
Topics: Rats; Mice; Animals; Microglia; Culture Media, Conditioned; Reflex, Startle; PC12 Cells
PubMed: 36333586
DOI: 10.1038/s41598-022-23571-5 -
Brain, Behavior, and Immunity Oct 2019The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to...
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for anxiety disorders, affective disorders, and trauma-and stressor-related disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and fear potentiation of the acoustic startle reflex. The acoustic startle reflex is an ethologically relevant reflex and can be potentiated in both humans and rats through Pavlovian conditioning. Mycobacterium vaccae is a soil-derived bacterium with immunoregulatory and anti-inflammatory properties that has been demonstrated to enhance fear extinction in the fear-potentiated startle paradigm when given prior to fear conditioning. To determine if immunization with M. vaccae after fear conditioning also has protective effects, adult male Sprague Dawley rats underwent fear conditioning on days -37 and -36 followed by immunizations (3x), once per week beginning 24 h following fear conditioning, with a heat-killed preparation of M. vaccae NCTC 11659 (0.1 mg, s.c., in 100 µl borate-buffered saline) or vehicle, and, then, 3 weeks following the final immunization, were tested in the fear-potentiated startle paradigm (n = 12 per group). Rats underwent fear extinction training on days 1 through 6 followed by spontaneous recovery 14 days later (day 20). Rats were euthanized on day 21 and brain tissue was sectioned for analysis of Tph2, Htr1a, Slc6a4, Slc22a3, and Crhr2 mRNA expression throughout the brainstem dorsal and median raphe nuclei. Immunization with M. vaccae did not affect fear expression on day 1. However, M. vaccae-immunized rats showed enhanced enhanced within-session fear extinction on day 1 and enhanced between-session fear extinction beginning on day 2, relative to vehicle-immunized controls. Immunization with M. vaccae and fear-potentiated startle had minimal effects on serotonergic gene expression when assessed 42 days after the final immunization. Together with previous studies, these data are consistent with the hypothesis that immunoregulatory strategies, such as immunization with M. vaccae, have potential for both prevention and treatment of trauma- and stressor-related psychiatric disorders.
Topics: Animals; Anxiety; Brain; Conditioning, Classical; Extinction, Psychological; Fear; Immunization; Inflammation; Male; Mycobacteriaceae; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Reflex, Startle; Stress Disorders, Post-Traumatic; Vaccination
PubMed: 31175996
DOI: 10.1016/j.bbi.2019.06.008 -
Human Brain Mapping Nov 2021Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the...
Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the startle reflex (prepulse precedes pulse by 30-500 ms), whereas Prepulse Facilitation (PPF) is the enhancement of the startle reflex (prepulse precedes pulse by 500-6000 ms). Here, we critically appraise human studies using functional neuroimaging to establish brain regions associated with PPI and PPF. Of 10 studies, nine studies revealed thalamic, striatal and frontal lobe activation during PPI in healthy groups, and activation deficits in the cortico-striato-pallido-thalamic circuitry in schizophrenia (three studies) and Tourette Syndrome (two studies). One study revealed a shared network for PPI and PPF in frontal regions and cerebellum, with PPF networks recruiting superior medial gyrus and cingulate cortex. The main gaps in the literature are (i) limited PPF research and whether PPI and PPF operate on separate/shared networks, (ii) no data on sex differences in neural underpinnings of PPI and PPF, and (iii) no data on neural underpinnings of PPI and PPF in other clinical disorders.
Topics: Functional Neuroimaging; Humans; Perception; Prepulse Inhibition; Reflex, Startle; Schizophrenia; Sensation; Tourette Syndrome
PubMed: 34414633
DOI: 10.1002/hbm.25631