scholarly journals Cocaine experience abolishes the motivation suppressing effect of CRF in the ventral midbrain

2019 ◽  
Author(s):  
Idaira Oliva ◽  
Melissa M. Donate ◽  
Merridee J. Lefner ◽  
Matthew J. Wanat

AbstractStress affects dopamine-dependent behaviors in part through the actions of corticotropin releasing factor (CRF) in the ventral tegmental area (VTA). For example, acute stress engages CRF signaling in the VTA to suppress the motivation to work for food rewards and promote drug seeking behavior. These diverging behavioral effects in food- and drug-based tasks could indicate that CRF modulates goal-directed actions in a reinforcer-specific manner. Alternatively, prior drug experience could functionally alter how CRF in the VTA regulates dopamine-dependent behavior. To address these possibilities, we examined how intra-VTA injections of CRF influenced cocaine intake and whether prior drug experience alters how CRF modulates the motivation for food rewards. Our results demonstrate that intra-VTA injections of CRF had no effect on drug intake when self-administering cocaine under a progressive ratio reinforcement schedule. We also found that a prior history of either contingent or non-contingent cocaine infusions abolished the capacity for CRF to reduce the motivation for food rewards. Furthermore, voltammetry recordings in the nucleus accumbens illustrate that CRF in the VTA had no effect on cocaine-evoked dopamine release. These results collectively illustrate that exposure to abused substances functionally alters how neuropeptides act within the VTA to influence motivated behavior.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristen A. McLaurin ◽  
Sarah J. Bertrand ◽  
Jessica M. Illenberger ◽  
Steven B. Harrod ◽  
Charles F. Mactutus ◽  
...  

AbstractMotivational deficits (e.g., apathy) and dysregulation (e.g., addiction) in HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor β agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for motivational alterations, however, has yet to be systematically evaluated. Thus, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed and drug-seeking behavior. First, at the genotypic level, motivational deficits in HIV-1 Tg rats treated with vehicle were characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose. Motivational dysregulation was evidenced by enhanced drug-seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated both motivational deficits and dysregulation in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited lower levels of dendritic branching and a shift towards longer dendritic spines with decreased head diameter. Treatment with SE, however, led to long-term enhancements in dendritic spine morphology in HIV-1 Tg animals supporting a potential underlying basis by which SE exerts its therapeutic effects. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.


2021 ◽  
Author(s):  
Kristen A. McLaurin ◽  
Sarah J. Bertrand ◽  
Jessica M. Illenberger ◽  
Steven B. Harrod ◽  
Charles F. Mactutus ◽  
...  

ABSTRACTThe persistence of motivational alterations, including apathy, in older HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor β agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for apathy, however, has yet to be systematically evaluated. Thus, beginning at approximately seven to nine months of age, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed behavior. First, at the genotypic level, apathetic behavior in older HIV-1 Tg rats treated with vehicle was characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose and enhanced drug seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated alterations in goal-directed behaviors and reduced drug seeking behavior in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited prominent decreases in dendritic branching and a shift towards longer dendritic spines with decreased head diameter; synaptic dysfunction that was partially restored by SE treatment. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.


2019 ◽  
Vol 16 (3) ◽  
pp. 250-257 ◽  
Author(s):  
Jiann-Der Lee ◽  
Ya-Han Hu ◽  
Meng Lee ◽  
Yen-Chu Huang ◽  
Ya-Wen Kuo ◽  
...  

Background and Purpose: Recurrent ischemic strokes increase the risk of disability and mortality. The role of conventional risk factors in recurrent strokes may change due to increased awareness of prevention strategies. The aim of this study was to explore the potential risk factors besides conventional ones which may help to affect the advances in future preventive concepts associated with one-year stroke recurrence (OSR). Methods: We analyzed 6,632 adult patients with ischemic stroke. Differences in clinical characteristics between patients with and without OSR were analyzed using multivariate logistic regression and classification and regression tree (CART) analyses. Results: Among the study population, 525 patients (7.9%) had OSR. Multivariate logistic regression analysis revealed that male sex (OR 1.243, 95% CI 1.025 – 1.506), age (OR 1.015, 95% CI 1.007 - 1.023), and a prior history of ischemic stroke (OR 1.331, 95% CI 1.096 – 1.615) were major factors associated with OSR. CART analysis further identified age and a prior history of ischemic stroke were important factors for OSR when classified the patients into three subgroups (with risks of OSR of 8.8%, 3.8%, and 12.5% for patients aged > 57.5 years, ≤ 57.5 years/with no prior history of ischemic stroke, and ≤ 57.5 years/with a prior history of ischemic stroke, respectively). Conclusions: Male sex, age, and a prior history of ischemic stroke could increase the risk of OSR by multivariate logistic regression analysis, and CART analysis further demonstrated that patients with a younger age (≤ 57.5 years) and a prior history of ischemic stroke had the highest risk of OSR.


2019 ◽  
pp. 217-220
Author(s):  
Eduardo Briceño-Souza ◽  
◽  
Nina Méndez-Domínguez ◽  
Ricardo j Cárdenas-Dajda ◽  
Walter Chin ◽  
...  

Diving as a method of fishing is used worldwide in small-scale fisheries. However, one of the main causes of morbidity and mortality among fishermen is decompression sickness (DCS). We report the case of a 46-year-old male fisherman diver who presented with chronic inguinal pain that radiated to the lower left limb. Living and working in a fishing port in Yucatan, he had a prior history of DCS. A diagnosis of avascular necrosis in the left femoral head secondary to DCS was made via analysis of clinical and radiological findings. The necrosis was surgically resolved by a total hip arthroplasty. Dysbaric osteonecrosis is a more probable diagnosis. In this region fishermen undergo significant decompression stress in their daily fishing efforts. Further studies regarding prevalence of dysbaric osteonecrosis among small-scale fisheries divers are needed. In a community where DCS is endemic and has become an epidemic, as of late, the perception of this health risk remains low. Furthermore, training and decompression technique are lacking among the fishing communities.


2016 ◽  
Vol 143 (1) ◽  
pp. 204-205
Author(s):  
J.S. Shah ◽  
A.J. Brown ◽  
N.D. Fleming ◽  
A.M. Nick ◽  
P.T. Soliman ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert J. Sanchez ◽  
Wenzhen Ge ◽  
Wenhui Wei ◽  
Manish P. Ponda ◽  
Robert S. Rosenson

Abstract Background This retrospective cohort study assessed the annualized incidence rate (IR) of acute pancreatitis (AP) in a nationally representative US adult population, as well as the variation in the risk of AP events across strata of triglyceride (TG) levels. Methods Data were obtained from IQVIA’s US Ambulatory Electronic Medical Records (EMR) database linked with its LRxDx Open Claims database. Inclusion criteria included ≥1 serum TG value during the overlapping study period of the EMR and claims databases, ≥1 claim in the 12-month baseline period, and ≥ 1 claim in the 12 months post index. All TG measurements were assigned to the highest category reached: < 2.26, ≥2.26 to ≤5.65, > 5.65 to ≤9.94, > 9.94, and > 11.29 mmol/L (< 200, ≥200 to ≤500, > 500 to ≤880, > 880, and > 1000 mg/dL, respectively). The outcome of interest was AP, defined as a hospitalization event with AP as the principal diagnosis. Results In total, 7,119,195 patients met the inclusion/exclusion criteria, of whom 4158 (0.058%) had ≥1 AP events in the prior 12 months. Most patients (83%) had TGs < 2.26 mmol/L (< 200 mg/dL), while < 1% had TGs > 9.94 mmol/L (> 880 mg/dL). Overall, the IR of AP was low (0.08%; 95% confidence internal [CI], 0.08–0.08%), but increased with increasing TGs (0.08% in TGs < 2.26 mmol/L [< 200 mg/dL] to 1.21% in TGs > 11.29 mmol/L [> 1000 mg/dL]). In patients with a prior history of AP, the IR of AP increased dramatically; patients with ≥2 AP events at baseline had an IR of 29.98% (95% CI, 25.1–34.9%). Conclusion The risk of AP increases with increasing TG strata; however, the risk increases dramatically among patients with a recent history of AP.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Florence Jaguga

Abstract Background Stuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors. Case presentation A 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms. Conclusion Clinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.


2021 ◽  
pp. 089719002110048
Author(s):  
Gregory G. Jackson ◽  
Christine R. Lopez ◽  
Elizabeth S. Bermudez ◽  
Nina E. Hill ◽  
Dan M. Roden ◽  
...  

Purpose: A case of loperamide-induced recurrent torsades de pointes is reported to raise awareness of an increasingly common phenomenon that could be encountered by medical providers during the current opioid epidemic. Summary: A 40 year-old-man with a prior history of opioid abuse who presented to the emergency department after taking up to 100 tablets of loperamide 2 mg daily for 5 years to blunt opioid withdrawal symptoms and was subsequently admitted to the intensive care unit for altered mental status and hyperthermia. The patient had prolonged QTc and 2 episodes of torsades de pointes (TdP) that resulted in cardiac arrest with return of spontaneous circulation. He was managed with isoproterenol, overdrive pacing, and methylnatrexone with no other events of TdP or cardiac arrest. Conclusion: A 40-year-old male who developed torsades de pointes from loperamide overdose effectively treated with overdrive pacing, isoproterenol, and methylnatrexone.


Sign in / Sign up

Export Citation Format

Share Document