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1.
Cogn Affect Behav Neurosci ; 19(6): 1404-1417, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31342271

RESUMO

Differences in the prevalence and presentation of psychiatric illnesses in men and women suggest that neurobiological sex differences confer vulnerability or resilience in these disorders. Rodent behavioral models are critical for understanding the mechanisms of these differences. Reward processing and punishment avoidance are fundamental dimensions of the symptoms of psychiatric disorders. Here we explored sex differences along these dimensions using multiple and distinct behavioral paradigms. We found no sex difference in reward-guided associative learning but a faster punishment-avoidance learning in females. After learning, females were more sensitive than males to probabilistic punishment but less sensitive when punishment could be avoided with certainty. No sex differences were found in reward-guided cognitive flexibility. Thus, sex differences in goal-directed behaviors emerged selectively when there was an aversive context. These differences were critically sensitive to whether the punishment was certain or unpredictable. Our findings with these new paradigms provide conceptual and practical tools for investigating brain mechanisms that account for sex differences in susceptibility to anxiety and impulsivity. They may also provide insight for understanding the evolution of sex-specific optimal behavioral strategies in dynamic environments.

2.
Neurobiol Dis ; 130: 104525, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31276792

RESUMO

Animal models that accurately recapitulate the accumulation of alpha-synuclein (α-syn) inclusions, progressive neurodegeneration of the nigrostriatal system and motor deficits can be useful tools for Parkinson's disease (PD) research. The preformed fibril (PFF) synucleinopathy model in rodents generally displays these PD-relevant features, however, the magnitude and predictability of these events is far from established. We therefore sought to optimize the magnitude of α-syn accumulation and nigrostriatal degeneration, and to understand the time course of both. Rats were injected unilaterally with different quantities of α-syn PFFs (8 or 16 µg of total protein) into striatal sites selected to concentrate α-syn inclusion formation in the substantia nigra pars compacta (SNpc). Rats displayed an α-syn PFF quantity-dependent increase in the magnitude of ipsilateral SNpc inclusion formation at 2 months and bilateral loss of nigral dopamine neurons at 6 months. Unilateral 16 µg PFF injection also resulted in modest sensorimotor deficits in forelimb adjusting steps associated with degeneration at 6 months. Bilateral injection of 16 µg α-syn PFFs resulted in symmetric bilateral degeneration equivalent to the ipsilateral nigral degeneration observed following unilateral 16 µg PFF injection (~50% loss). Bilateral PFF injections additionally resulted in alterations in several gait analysis parameters. These α-syn PFF parameters can be applied to generate a reproducible synucleinopathy model in rats with which to study pathogenic mechanisms and vet potential disease-modifying therapies.

3.
J Clin Lipidol ; 13(3): 443-454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31076261

RESUMO

BACKGROUND: Patients with prior cardiovascular events are at very high risk of recurrent events and may benefit from low-density lipoprotein cholesterol (LDL-C) lowering beyond that achieved with maximally tolerated statins. OBJECTIVE: To assess potential differences between the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor, alirocumab, in patients with vs without prior myocardial infarction (MI)/ischemic stroke. METHODS: Data (n = 4880) were pooled from nine ODYSSEY phase 3 trials of alirocumab 75/150 mg or 150 mg every 2 weeks, mostly on background statins ± other lipid-lowering therapies. Analyses were performed according to statin status, alirocumab dose, and control (placebo or ezetimibe). RESULTS: Baseline LDL-C, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B levels were lower and lipoprotein(a) higher in patients with than without prior MI/ischemic stroke. LDL-C levels were reduced from baseline to week 24 in patients with (51.1%-62.9%) and without (43.6%-58.3%) prior MI/ischemic stroke, with no significant interaction between prior MI/ischemic stroke status and LDL-C-lowering efficacy of alirocumab vs controls. Alirocumab significantly reduced other lipid/lipoproteins (including lipoprotein[a]) similarly in patients with/without MI/ischemic stroke. Week 24 LDL-C goal attainment rates for subgroups with/without prior MI/ischemic stroke on background statins were 74.1%-84.8% and 63.7%-74.7%, respectively. The safety profile of alirocumab was generally similar regardless of prior MI/ischemic stroke status. CONCLUSIONS: Alirocumab significantly reduced LDL-C and other atherogenic lipids/lipoproteins in patients with prior MI/ischemic stroke, and the majority of this very high cardiovascular risk population achieved LDL-C goals; efficacy and safety results were similar in patients without prior MI/ischemic stroke.

4.
Hum Mutat ; 40(6): 816-827, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870574

RESUMO

Pyruvate carboxylase deficiency (PCD) is caused by biallelic mutations of the PC gene. The reported clinical spectrum includes a neonatal form with early death (type B), an infantile fatal form (type A), and a late-onset form with isolated mild intellectual delay (type C). Apart from homozygous stop-codon mutations leading to type B PCD, a genotype-phenotype correlation has not otherwise been discernible. Indeed, patients harboring biallelic heterozygous variants leading to PC activity near zero can present either with a fatal infantile type A or with a benign late onset type C form. In this study, we analyzed six novel patients with type A (three) and type C (three) PCD, and compared them with previously reported cases. First, we observed that type C PCD is not associated to homozygous variants in PC. In silico modeling was used to map former and novel variants associated to type A and C PCD, and to predict their potential effects on the enzyme structure and function. We found that variants lead to type A or type C phenotype based on the destabilization between the two major enzyme conformers. In general, our study on novel and previously reported patients improves the overall understanding on type A and C PCD.

5.
Methods Mol Biol ; 1937: 3-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706387

RESUMO

Today any researcher with the desire can easily purchase a viral vector. However, despite the availability of viral vectors themselves, the requisite knowledge that is absolutely essential to conducting a gene therapy experiment remains somewhat obscure and esoteric. To utilize viral vectors to their full potential, a large number of decisions must be made, in some instances prior to even obtaining the vector itself. For example, critical decisions include selection of the proper virus, selection of the proper expression cassette, whether to produce or purchase a viral vector, proper viral handling and storage, the most appropriate delivery method, selecting the proper controls, how to ensure your virus is expressing properly, and many other complex decisions that are essential to performing a successful gene therapy experiment. The need to make so many important decisions can be overwhelming and potentially prohibitive, especially to the novice gene therapist. In order to aid in this challenging process, here we provide an overview of basic gene therapy modalities and a decision tree that can be used to make oneself aware of the options available to the beginning gene therapist. This information can be used as a road map to help navigate the complex and perhaps confusing process of designing a successful gene therapy experiment.


Assuntos
Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Adenoviridae/genética , Animais , Tomada de Decisões , Dependovirus/genética , Expressão Gênica , Vetores Genéticos/fisiologia , Humanos , Lentivirus/genética , Simplexvirus
6.
Genet Med ; 21(9): 2036-2042, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739909

RESUMO

PURPOSE: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients. METHODS: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information. RESULTS: The cohort of 27 patients all had novel variants, and ranged in age from 2 to 68 years. All had developmental delay/intellectual disability. Autism spectrum disorders/autistic features were reported in 69%, attention disorders or hyperactivity in 67%, craniofacial features (no recognizable facial gestalt) in 67%, structural brain anomalies in 24%, and seizures in 12%. Additional features affecting various organ systems were described in 93%. In a majority of patients, we did not observe previously reported findings of postnatal overgrowth or craniosynostosis, in comparison with earlier reports. CONCLUSION: We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20.

7.
Body Image ; 28: 44-52, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30580168

RESUMO

This study investigated how exposure to non-body focused others (i.e., those who are not preoccupied with their body weight/shape or appearance) and exposure to body focused others uniquely affect young women's eating and body image over a week, within a day, and from one day to the next. For seven consecutive days, 92 female college students completed nightly online questionnaires about their daily experiences. Between-persons, multilevel modelling revealed that higher average levels of exposure to non-body focused others over the week uniquely predicted greater intuitive eating, greater body appreciation, and less dietary restraint, whereas higher average exposure to body focused others predicted these outcomes in the opposite direction. Within-persons, exposure to body focused others did not predict eating and body image, but exposure to non-body focused others did. On days when women had more exposure to non-body focused others than their personal average level or than the previous day's level, eating and body image were better. These findings are the first to suggest that independent of exposure to body focused others, level of exposure to non-body focused others - within and across days - contribute positively to eating and body image.


Assuntos
Imagem Corporal/psicologia , Comportamento Alimentar/psicologia , Relações Interpessoais , Estudantes/psicologia , Adulto , Feminino , Humanos , Universidades , Adulto Jovem
8.
Am J Perinatol ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396229

RESUMO

OBJECTIVE: We sought to evaluate differences in pregnancy outcomes following early amniotomy in women with class III obesity (body mass index ≥40 kg/m2) undergoing induction of labor. STUDY DESIGN: This is a retrospective cohort study of women with class III obesity undergoing term induction of labor from January 2007 to February 2013. Early amniotomy was defined as artificial membrane rupture at less than 4 cm cervical dilation. The primary outcome was cesarean delivery. Secondary outcomes included length of labor, a maternal morbidity composite, and a neonatal morbidity composite. A subgroup analysis examined the effect of parity. Multivariable logistic regression was used to adjust for covariates. RESULTS: Of 285 women meeting inclusion criteria, 107 (37.5%) underwent early amniotomy and 178 (62.5%) underwent late amniotomy. Early amniotomy was associated with cesarean delivery after multivariable adjustments (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.21-3.47). There were no significant differences in length of labor or maternal and neonatal morbidity between groups. When stratified by parity, early amniotomy was associated with increased cesarean delivery (aOR, 3.10; 95% CI, 1.47-6.58) only in nulliparous women. CONCLUSION: Early amniotomy among class III obese women, especially nulliparous women, undergoing labor induction may be associated with an increased risk of cesarean delivery.

10.
Pediatrics ; 142(5)2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30315121

RESUMO

An infant with complex congenital heart disease suffers a prolonged cardiac arrest with minutes of anoxia. He is left with severe brain damage and profound neurologic impairment. He no longer responds to caregivers. Much of the time, he cries and grimaces as if in pain. He has required increasing sedation to control these symptoms. His parents live hours from the hospital and seldom visit. When their infant's situation is explained to them over the telephone, they request that doctors "do everything to keep him alive." His bedside caregivers report high levels of moral and psychological distress and frequently discuss J.S.'s "suffering." An ethics consultation is requested, asking whether it is permissible to withdraw life support despite the parents' request that therapy continue.

11.
Aust Occup Ther J ; 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30298927

RESUMO

BACKGROUND/AIM: Assessment of cognitive function in people with neurosychiatric disorders can be challenging, due to behavioural and psychiatric symptomatology. The Behavioural Assesment Tool for Cognition and Higher Functioning (BATCH) is a validated observational tool that complements formal cognitive testing in this patient population. This study aimed to determine the capacity of the BATCH as a predictive tool for discharge planning. METHOD: BATCH scores for 330 consecutive admissions for assessment to a specialist neuropsychiatry unit between 2007 and 2015 were analysed. The variables of interest included discharge destination, diagnosis, length of stay, age at discharge and BATCH scores (both subdomain and total). Significant predictors of discharge destination were identified using logistic regression analysis. RESULTS: After adjusting for age at discharge, three variables were found to be significant predictors of discharge destination - length of stay, diagnosis, and BATCH total score. The odds of being discharged to a destination other than home decreased by 3% for each additional BATCH total score unit. The length of stay remained a significant predictor of discharge destination when adjusting for BATCH total score, age at admission and diagnosis. CONCLUSION: BATCH total scores, but not subdomain scores, were predictive of discharge destination, along with the patients' length of stay and diagnosis. Knowledge of this relationship may guide clinical discharge planning, when working with the complex needs of this group of patients. A larger study is indicated to determine the range and cut-off scores for discharge destinations other than home.

12.
Biomed Opt Express ; 9(6): 2871-2886, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30258696

RESUMO

Diffuse reflectance spectroscopy (DRS) has been used in murine studies to quantify tumor perfusion and therapeutic response. These studies frequently use inhaled isoflurane anesthesia, which depresses the respiration rate and results in the desaturation of arterial oxygen saturation, potentially affecting tissue physiological parameters. However, there have been no controlled studies quantifying the effect of isoflurane anesthesia on DRS-derived physiological parameters of murine tissue. The goal of this study was to perform DRS on Balb/c mouse (n = 10) tissue under various anesthesia conditions to quantify effects on tissue physiological parameters, including total hemoglobin concentration, tissue oxygen saturation, oxyhemoglobin and reduced scattering coefficient. Two independent variables were manipulated including metabolic gas type (pure oxygen vs. medical air) and isoflurane concentration (1.5 to 4.0%). The 1.5% isoflurane and 1 L/min oxygen condition most closely mimicked a no-anesthesia condition with oxyhemoglobin concentration within 89% ± 19% of control. The time-dependent effects of isoflurane anesthesia were tested, revealing that anesthetic induction with 4.0% isoflurane can affect DRS-derived physiological parameters up to 20 minutes post-induction. Finally, spectroscopy with and without isoflurane anesthesia was compared for colon tumor Balb/c-CT26 allografts (n = 5) as a representative model of subcutaneous murine tumor allografts. Overall, isoflurane anesthesia yielded experimentally-induced depressed oxyhemoglobin, and this depression was both concentration and time dependent. Investigators should understand the dynamic effects of isoflurane on tissue physiological parameters measured by DRS. These results may guide investigators in eliminating, limiting, or managing anesthesia-induced physiological changes in DRS studies in mouse models.

13.
Neurourol Urodyn ; 37(8): 2860-2866, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30168627

RESUMO

AIMS: To compare surgical success rates in older versus younger women a minimum of 3 years post transvaginal native tissue repair for apical prolapse. Post-operative symptom severity and quality of life improvement, surgical complications and retreatment were also examined. METHODS: Women who underwent transvaginal native tissue repair for apical prolapse between 2011 and 2013 were eligible. Subjects completed the pelvic floor distress inventory (PFDI-20), pelvic floor impact questionnaire (PFIQ-7), and patient global impression of improvement (PGI-I), and were categorized as "younger" (age <70) or "older" (age ≥70). The primary outcome of surgical success was defined as the absence of bulge symptoms and no re-treatment for prolapse. RESULTS: Of 641 eligible patients, response rate was 51.0%. 62.7% of subjects had hysterectomy prior to index surgery. Surgical success was noted in 72.9% of younger and 82.2% of older subjects (Adjusted odds ratio [aOR] 1.72, 95% CI [0.93, 3.17]). Older women had greater improvement from baseline in PFDI-20 score (-87.5 [IQR 74.0] vs -54.2 [IQR 80.2], P = 0.01). Retreatment rate and surgical complication rates were similar between groups (both P > 0.05). CONCLUSIONS: Older and younger women had similar surgical success rates a minimum of 3 years post-operative; however, older women had a greater overall symptom severity improvement. This information may be helpful in counseling older women regarding surgical expectations and decision-making.

14.
Genet Med ; 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30206421

RESUMO

PURPOSE: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences. METHODS: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms. RESULTS: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments. CONCLUSION: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.

15.
Wellcome Open Res ; 3: 46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29900417

RESUMO

Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novoDNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29922228

RESUMO

Multiple lines of evidence indicate that androgens, such as testosterone, modulate the mesocorticolimbic system and executive function. This review integrates neuroanatomical, molecular biological, neurochemical, and behavioral studies to highlight how endogenous and exogenous androgens alter behaviors, such as behavioral flexibility, decision making, and risk taking. First, we briefly review the neuroanatomy of the mesocorticolimbic system, which mediates executive function, with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Second, we present evidence that androgen receptors (AR) and other steroid receptors are expressed in the mesocorticolimbic system. Using sensitive immunohistochemistry and quantitative polymerase chain reaction (qPCR) techniques, ARs are detected in the VTA, NAc, mPFC, and OFC. Third, we describe recent evidence for local androgens ("neuroandrogens") in the mesocorticolimbic system. Steroidogenic enzymes are expressed in mesocorticolimbic regions. Furthermore, following long-term gonadectomy, testosterone is nondetectable in the blood but detectable in the mesocorticolimbic system, using liquid chromatography tandem mass spectrometry. However, the physiological relevance of neuroandrogens remains unknown. Fourth, we review how anabolic-androgenic steroids (AAS) influence the mesocorticolimbic system. Fifth, we describe how androgens modulate the neurochemistry and structure of the mesocorticolimbic system, particularly with regard to dopaminergic signaling. Finally, we discuss evidence that androgens influence executive functions, including the effects of androgen deprivation therapy and AAS. Taken together, the evidence indicates that androgens are critical modulators of executive function. Similar to dopamine signaling, there might be optimal levels of androgen signaling within the mesocorticolimbic system for executive functioning. Future studies should examine the regulation and functions of neurosteroids in the mesocorticolimbic system, as well as the potential deleterious and enduring effects of AAS use.

17.
Cancer Metab ; 6: 6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854399

RESUMO

Background: Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of the glycolytic enzyme pyruvate kinase. PKM2 expression is associated with embryogenesis, tissue regeneration, and cancer. PKM2 is also the pyruvate kinase isoform expressed in most wild-type adult tissues, with PKM1 restricted primarily to skeletal muscle, heart, and brain. To interrogate the functional requirement for PKM2 during tumor initiation in an autochthonous mouse model for soft tissue sarcoma (STS), we used a conditional Pkm2 allele (Pkm2fl ) to abolish PKM2 expression. Results: PKM2 deletion slowed tumor onset but did not abrogate eventual tumor outgrowth. PKM2-null sarcoma cells expressed PKM1 with tumors containing a high number of infiltrating PKM2 expressing stromal cells. End-stage PKM2-null tumors showed increased proliferation compared to tumors with a wild-type Pkm2 allele, and tumor metabolite analysis revealed metabolic changes associated with PKM2 loss. Conclusions: While PKM2 is not required for soft tissue sarcoma growth, PKM2 expression may facilitate initiation of this tumor type. Because these data differ from what has been observed in other cancer models where PKM2 has been deleted, they argue that the consequences of PKM2 loss during tumor initiation are dependent on the tumor type.

18.
Behav Neurosci ; 132(3): 152-160, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29809043

RESUMO

Anabolic-androgenic steroid (AAS) abuse is implicated in maladaptive decision making such as increased risk taking and problem gambling. Endogenous testosterone correlates with economic risk taking in both the stock market (Coates & Herbert, 2008) and in the laboratory, as measured by the Iowa Gambling Task (Stanton, Liening, & Schultheiss, 2011). Additionally, AAS use has been associated with problem gambling behavior in adolescents (Proimos, DuRant, Pierce, & Goodman, 1998). Thus, AAS may impair economic decision making. However, studies of human AAS users cannot control for preexisting risky behavior or normalize androgen levels. Accordingly, the present study investigated AAS effects on decision making in rats using a novel, balanced rodent model of the IGT. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water) sc, and trained to work for sugar pellets in an operant chamber equipped with 4 levers, each associated with a different schedule of reward magnitude (number of pellets), probability, and punishment (time-out) duration. By RM-ANOVA, there was a main effect of lever (F3,78 = 25.33, p < .05), such that all rats preferred lever L4 offering a large reward (4 pellets), but with low probability (45%) and a long (35 sec) time-out. There was also a significant interaction of testosterone × lever (F3,78 = 2.78, p < .05), with testosterone increasing preference for L4 and decreasing preference for the other levers, relative to vehicle-treated controls. These data extend our previous findings of altered decision making in AAS-treated rats, and suggest that AAS may alter economic decision making in human users. (PsycINFO Database Record

19.
Psychopharmacology (Berl) ; 235(4): 959-969, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29242988

RESUMO

BACKGROUND: Anabolic-androgenic steroid abuse is implicated in maladaptive behaviors such as impaired cognition in humans. In a rat model, our lab has shown that testosterone decreases preference for a large/uncertain reward in probability discounting. Other studies have shown that androgens decrease dopamine D1 and D2 receptors in the nucleus accumbens shell, a region important for decision-making behavior in probability discounting. Thus, we attempted to restore selection of the large/uncertain reward in testosterone-treated rats by administering the D2 receptor agonist quinpirole or the D1 receptor agonist SKF81297 and testing probability discounting. METHODS: Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water), and tested for probability discounting after injections of saline, 0.1 and 0.5 mg/kg of quinpirole or SKF81297. Rats chose between a small/certain reward (1 sugar pellet, 100% probability) and a large/uncertain reward (4 pellets, decreasing probability: 100, 75, 50, 25, 0%). RESULTS: Testosterone-treated rats selected the large/uncertain reward significantly less than vehicle-treated controls after saline injection. However, acute injection with 0.1 mg/kg quinpirole increased large/uncertain reward preference in testosterone-treated rats only, indicated by a testosterone × quinpirole interaction. At 0.5 mg/kg, quinpirole increased large/uncertain reward preference in all rats. Acute injection with SKF81297 at 0.1 or 0.5 mg/kg rescued large/uncertain reward preference in testosterone-treated rats by eliminating the difference between groups. CONCLUSIONS: It appears that altered probability discounting behavior in testosterone-treated rats is due to both decreased D1 and D2 receptor function.

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