Motivated behavior can be characterized by behavioral activation and high work output. Moreover, people with depression and other disorders show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Effort-based decision making is studied using tasks offering choices between high effort options leading to highly valued reinforcers vs low effort/low reward options, and such tasks could be useful as animal models of motivational symptoms. In the present studies the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ) were investigated. TBZ blocks vesicular storage and also produces depressive symptoms in humans. Moreover, TBZ alters effort-based choice in rats, biasing animals toward low effort alternatives. The present studies investigated the ability of acute administration of various monoamine uptake inhibitors to reverse the effects of TBZ. Effort-related effects of TBZ were attenuated by the catecholamine uptake inhibitor and antidepressant bupropion, and this effect of bupropion was reversed by either D1 or D2 family antagonism. The effort-related effects of TBZ were also attenuated by the selective dopamine uptake blocker GBR12909. The 5-HT uptake inhibitor fluoxetine and the norepinephrine uptake inhibitor desipramine failed to reverse the effects of TBZ, and higher doses of these drugs, given alone or in combination with TBZ, led to further behavioral impairments. These results indicate that drugs acting on dopamine transmission are relatively effective at reversing the effort-related effects of TBZ, and are consistent with the hypothesis that drugs that enhance dopamine transmission may be effective at treating effort-related psychiatric symptoms in humans.

Dyslexia is a learning disability characterized by difficulty learning to read and write. The underlying biological and genetic etiology remains poorly understood. One candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1), has been shown to be associated with deficits in short-term memory in dyslexic populations. The purpose of the current study was to examine the behavioral phenotype of a mouse model with a homozygous conditional (forebrain) knockout of the rodent homolog Dyx1c1. Twelve Dyx1c1 conditional homozygous knockouts, 7 Dyx1c1 conditional heterozygous knockouts and 6 wild-type controls were behaviorally assessed. Mice with the homozygous Dyx1c1 knockout showed deficits on memory and learning, but not on auditory or motor tasks. These findings affirm existing evidence that DYX1C1 may play an underlying role in the development of neural systems important to learning and memory, and disruption of this function could contribute to the learning deficits seen in individuals with dyslexia.

The cardinal motor symptoms of Parkinson's disease (PD) include resting tremor, akinesia, bradykinesia, and rigidity, and these motor abnormalities can be modeled in rodents by administration of the VMAT-2 (type-2 vesicular monoamine transporter) inhibitor tetrabenazine (9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7, 11b hexahydrobenzo[a]quinolizin-2-one; TBZ). Depression is also commonly associated with PD, and clinical data indicate that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine ((±)-N-methyl-γ-[4-(trifluoromethyl)phenoxy]benzenepropanamine hydrochloride; FLX) are frequently used to treat depression in PD patients. The aim of the present study was to characterize the effect of FLX on the motor dysfunctions induced by a low dose of TBZ (0.75 mg/kg), and investigate the neural mechanisms involved. This low dose of TBZ was selected based on studies with rat models of depressive symptoms. In rats, coadministration of FLX (2.5, 5.0, and 10.0 mg/kg) increased TBZ-induced oral tremor (tremulous jaw movements), and decreased locomotor activity compared with administration of TBZ alone. Coadministration of the serotonin 5-HT2A/2C antagonist mianserin (2.5 and 5.0 mg/kg) attenuated the increase in oral tremor induced by coadministration of TBZ (0.75 mg/kg) with FLX (5.0 mg/kg). Consistent with these behavioral data, coadministration of TBZ and FLX decreased DA tissue levels in the rat ventrolateral neostriatum compared with TBZ alone, and coadministration of mianserin with TBZ and FLX attenuated this effect, increasing DA tissue levels compared with the TBZ/FLX condition. These data suggest that SSRI administration in PD patients may result in worsening of motor symptoms, at least in part, by exacerbating existing DA depletions through 5-HT2A/2C-mediated modulation of DA neurotransmission.

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Introduction: The COVID-19 pandemic has caused major changes to healthcare services, especially those related to early detection and screening practices like breast cancer. In Puerto Rico, breast cancer is the main cause of death, representing 18.9% of cancer deaths in women, making early detection even more important to prevent morbidity and mortality. This study aims to describe the impact of COVID-19 on breast cancer screening and assess differences in health utilization by age group and health regions in Puerto Rico. Methods: This study used data on breast cancer screening medical claims from Puerto Rico Track, a project in collaboration with the Puerto Rico Public Health System and the Puerto Rico Institute of Statistics that aims to assess health access and utilization patterns in Puerto Rico. Claims including unilateral and bilateral mammography, sonommamography, and MRI were analyzed. Descriptive statistics and percentual changes between the COVID-19 baseline year (2016) compared with 2020 and 2021 were performed (overall, by age-group and health region). Results: A total of 193,793 screening tests were performed in 2016, compared to 66,463 in 2020, and 89,322 in 2021. Overall, a third of the medical claims for breast cancer screening (33.2%) were in the age group of 51-60 years. An overall decreasing percentual change was observed comparing 2016 vs. 2020 (65.7%), where the age group with the broadest gap reduction were among women 41-50 years old (68.2%). When comparing medical claims of 2016 (193,750) versus 2021 (89,320) (pre and post pandemic), an important decreasing change (53.9%) was observed. The age group with the highest decrease comparing 2016 to 2021 was the 41-50 years one (68.2%). The Western region of Mayagüez/Aguadilla had the highest decreasing percentual change, with a reduction of 73.6% in 2020 compared to 2016, and 62.6% when compared 2021 with 2016. Conclusion: Breast cancer screening was notably affected by the COVID-19 pandemic in Puerto Rico. A pattern of decreasing breast cancer screening was observed by health regions and by age. These efforts provide evidence of the need of tailored evidence-based interventions to increase breast cancer screening in the island. Citation Format: Vivian Colón-López, Hermilis Berrios Ortiz, Hector Contreras-Mora, Orville M. Disdier, Cynthia M. Pérez, Nilda Ríos, Olga L. Díaz, Juan Mejías, Erick L. Suárez-Pérez. Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 799.