scholarly journals Persistent vulnerability to relapse despite complete extinction of cocaine craving

2016 ◽  
Author(s):  
Paul Girardeau ◽  
Sylvia Navailles ◽  
Audrey Durand ◽  
Caroline Vouillac-Mendoza ◽  
Karine Guillem ◽  
...  
Keyword(s):  
Relapse Prevention ◽  
Research Effort ◽  
Brain Regions ◽  
Self Administration ◽  
Preclinical Development ◽  
Complete Extinction ◽  
Prevention Interventions ◽  
Cocaine Craving ◽  
Novel Target

ABSTRACTCraving often precedes relapse into cocaine addiction. This explains why considerable research effort is being expended to try to develop anti-craving strategies for relapse prevention. Recently, we discovered using the classic reinstatement model of cocaine craving that the reinstating or priming effect of cocaine can be extinguished with repeated priming in rats - a phenomenon dubbed extinction of cocaine priming. Here we sought to measure the potential beneficial effect of this novel extinction strategy on subsequent relapse (i.e., return to the pre-extinction pattern of cocaine self-administration once the drug is made again available after extinction). Overall and contrary to our initial hope, extensive and complete extinction of cocaine priming had no major impact on relapse. This lack of effect occurred despite evidence for post-extinction loss of neuronal responses to cocaine priming in brain regions critically involved in cocaine-induced reinstatement (i.e., the dorsomedial prefrontal cortex and the core of the nucleus accumbens). An effect of extinction of cocaine priming on relapse was only observed when cocaine was available for self-administration under more demanding conditions. However, this effect was modest and short-lived. Finally, we succeeded to trace the origin of our failure to prevent relapse to a persistent, extinction-resistant form of operant behavior that is not directly induced by cocaine. This extinction-resistant behavior is commonly reported, though generally ignored as causally irrelevant, in many other reinstatement studies. We propose that this behavior should become both a novel marker for long-term vulnerability to relapse and a novel target for preclinical development of potential relapse prevention interventions.

scholarly journals Effects of long-term cocaine self-administration on brain resting-state functional connectivity in nonhuman primates

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen J. Kohut ◽  
Dionyssios Mintzopoulos ◽  
Brian D. Kangas ◽  
Hannah Shields ◽  
Kelly Brown ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Cognitive Processing ◽  
Resting State ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Resting State Functional Connectivity ◽  
Self Administration ◽  
Chronic Cocaine

AbstractLong-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen—two brain regions involved in cognitive function and motoric behavior—identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299–424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.

Long-Term Effects of HIV Prevention Interventions With African American Crack-Using Women

2006 ◽  
Author(s):  
Wendee M. Wechsberg ◽  
Wendy K. K. Lam ◽  
Rhonda S. Karg ◽  
Kara Riehman ◽  
Kyla M. Sawyer
Keyword(s):  
African American ◽  
Hiv Prevention ◽  
Long Term Effects ◽  
Prevention Interventions ◽  
Hiv Prevention Interventions

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

scholarly journals Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 287
Author(s):  
Maria Isabella Donegani ◽  
Alberto Miceli ◽  
Matteo Pardini ◽  
Matteo Bauckneht ◽  
Silvia Chiola ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Structural Connectivity ◽  
Statistical Parametric Mapping ◽  
Brain Regions ◽  
Olfactory Dysfunction ◽  
Whole Body ◽  
Mapping Software ◽  
18F Fdg ◽  
Left Insula

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.

scholarly journals The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Hippocampal Field ◽  
Power Spectral ◽  
Density Values ◽  
Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

2021 ◽  
Vol 79 (4) ◽  
pp. 1701-1711
Author(s):  
Tetsuo Hayashi ◽  
Shotaro Shimonaka ◽  
Montasir Elahi ◽  
Shin-Ei Matsumoto ◽  
Koichi Ishiguro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Brain ◽  
Functional Decline ◽  
Brain Regions ◽  
Insoluble Fraction ◽  
Brain Extract ◽  
Post Injection ◽  
Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

scholarly journals Withdrawal from long-term methamphetamine self-administration ‘normalizes’ neurometabolites in rhesus monkeys: a1H MR spectroscopy study

2013 ◽  
Vol 20 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Shaolin Yang ◽  
Annabelle M. Belcher ◽  
Svetlana Chefer ◽  
D. Bruce Vaupel ◽  
Charles W. Schindler ◽  
...  
Keyword(s):  
Mr Spectroscopy ◽  
Rhesus Monkeys ◽  
Spectroscopy Study ◽  
Self Administration

scholarly journals Fundamental Dynamical Modes Underlying Human Brain Synchronization

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Catalina Alvarado-Rojas ◽  
Michel Le Van Quyen
Keyword(s):  
Large Scale ◽  
Brain Regions ◽  
Electrode Placement ◽  
High Dimensional ◽  
Sleep Cycle ◽  
Epileptic Patients ◽  
Brain States ◽  
Intracranial Recordings ◽  
Characteristic Dynamic

Little is known about the long-term dynamics of widely interacting cortical and subcortical networks during the wake-sleep cycle. Using large-scale intracranial recordings of epileptic patients during seizure-free periods, we investigated local- and long-range synchronization between multiple brain regions over several days. For such high-dimensional data, summary information is required for understanding and modelling the underlying dynamics. Here, we suggest that a compact yet useful representation is given by a state space based on the first principal components. Using this representation, we report, with a remarkable similarity across the patients with different locations of electrode placement, that the seemingly complex patterns of brain synchrony during the wake-sleep cycle can be represented by a small number of characteristic dynamic modes. In this space, transitions between behavioral states occur through specific trajectories from one mode to another. These findings suggest that, at a coarse level of temporal resolution, the different brain states are correlated with several dominant synchrony patterns which are successively activated across wake-sleep states.

scholarly journals Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration

2011 ◽  
Vol 669 (1-3) ◽  
pp. 71-75 ◽  
Author(s):  
Stanley D. Glick ◽  
Elizabeth M. Sell ◽  
Sarah E. McCallum ◽  
Isabelle M. Maisonneuve
Keyword(s):  
Brain Regions ◽  
Self Administration

The Long-Term Effects of Mindfulness-Based Cognitive Therapy as a Relapse Prevention Treatment for Major Depressive Disorder

2010 ◽  
Vol 38 (5) ◽  
pp. 561-576 ◽  
Author(s):  
Kate L. Mathew ◽  
Hayley S. Whitford ◽  
Maura A. Kenny ◽  
Linley A. Denson
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cognitive Therapy ◽  
Relapse Prevention ◽  
Mindfulness Practice ◽  
Long Term Effects ◽  
Major Depressive ◽  
Strong Negative Correlation ◽  
Group 3

Background: Mindfulness-based Cognitive Therapy (MBCT) is a relapse prevention treatment for major depressive disorder. Method: An observational clinical audit of 39 participants explored the long-term effects of MBCT using standardized measures of depression (BDI-II), rumination (RSS), and mindfulness (MAAS). Results: MBCT was associated with statistically significant reductions in depression from pre to post treatment. Gains were maintained over time (Group 1, 1–12 months, p = .002; Group 2, 13–24 months, p = .001; Group 3, 25–34 months, p = .04). Depression scores in Group 3 did begin to worsen, yet were still within the mild range of the BDI-II. Treatment variables such as attendance at “booster” sessions and ongoing mindfulness practice correlated with better depression outcomes (p = .003 and p = .03 respectively). There was a strong negative correlation between rumination and mindful attention (p < .001), consistent with a proposed mechanism of metacognition in the efficacy of MBCT. Conclusion: It is suggested that ongoing MBCT skills and practice may be important for relapse prevention over the longer term. Larger randomized studies of the mechanisms of MBCT with longer follow-up periods are recommended.

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