Long-Term Fluoxetine Treatment Modulates Cannabinoid Type 1 Receptor-Mediated Inhibition of Adenylyl Cyclase in the Rat Prefrontal Cortex through 5-Hydroxytryptamine1A Receptor-Dependent Mechanisms

2009 ◽  
Vol 77 (3) ◽  
pp. 424-434 ◽  
Author(s):  
Susana Mato ◽  
Rebeca Vidal ◽  
Elena Castro ◽  
Álvaro Díaz ◽  
Ángel Pazos ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Adenylyl Cyclase ◽  
Cannabinoid Type 1 Receptor ◽  
Fluoxetine Treatment

scholarly journals Long-term decreased cannabinoid type-1 receptor activity restores specific neurological phenotypes in the Ts65Dn mouse model of Down syndrome

2021 ◽  
Author(s):  
Anna Vazquez-Oliver ◽  
Silvia Perez-Garcia ◽  
Nieves Pizarro ◽  
Laura Molina-Porcel ◽  
Rafael de la Torre ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Side Effects ◽  
Mouse Model ◽  
Neurological Deficits ◽  
Wild Type ◽  
Male And Female ◽  
Cannabinoid Type 1 Receptor ◽  
Cognitive Improvement

Intellectual disability is the most prevalent and limiting hallmark of Down syndrome (DS), without any pharmacological treatment available. Neurodegeneration and neuroinflammation are relevant neurological features of DS reaching to early development of Alzheimer s disease. Preclinical evidence suggests that the endocannabinoid system, an important neuromodulator on cognition and neuroinflammation, could act as beneficial target in DS. Indeed, cannabinoid type-1 receptor (CB1R) activity was enhanced in the hippocampus of young-adult trisomic Ts65Dn mice, a well-characterized surrogate model of DS. In previous studies, inhibition of CB1R, was able to restore key neurological deficits in this mouse model. To determine the possible clinical relevance of this target, it is mandatory to evaluate the long-term consequences of attenuated CB1R activity and to minimize the possible side-effects associated to this mechanism. We found that CB1R expression was significantly enhanced in the hippocampus brains of aged DS subjects. Similarly, middle-aged trisomic mice showed enhanced CB1R expression. Long-term oral administration of a low dose of the CB1R specific antagonist rimonabant was administered to male and female Ts65Dn trisomic and wild-type mice from the time of weaning to 10 months, an age when signs of neurodegeneration have been described in the model. CB1R inhibition resulted in significant cognitive improvement in novel object-recognition memory in trisomic male and female mice, reaching a similar performance to that of wild-type littermates. Interestingly, this long-term rimonabant treatment modify locomotor activity, anxiety-like behavior, body weight or survival rates. Brain analysis at 10 months of age revealed noradrenergic and cholinergic neurodegeneration signs in trisomic mice that were not modified by the treatment, although the alterations in hippocampal microglia morphology shown by vehicle-treated trisomic mice was normalized in trisomic mice exposed to rimonabant. Altogether, our results demonstrate a sustained pro-cognitive effect of CB1R inhibition at doses that do not produce major side effects that could be associated to an anti-inflammatory action, suggesting a potential interest in this target of to preserve cognitive functionality in DS.

scholarly journals Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alexander O. Shpakov ◽  
Kira V. Derkach ◽  
Irina V. Moyseyuk ◽  
Oksana V. Chistyakova
Keyword(s):  
Adenylyl Cyclase ◽  
Serotonin Receptor ◽  
Streptozotocin Diabetes ◽  
Male Rats ◽  
Intranasal Insulin ◽  
Polypeptide Hormones ◽  
Hormone Sensitive ◽  
Serotonin Receptor Agonists

One of the causes of complications in type 1 diabetes mellitus (T1DM) is the changes in adenylyl cyclase (AC) signaling system, identified on the early stages of the disease. However, the most significant disturbances in this system occur on the later stages of T1DM, which ultimately leads to severe complications, but functional state of the AC system in late T1DM is poorly understood. The aim of this work was to study alterations in AC system sensitive to biogenic amines and polypeptide hormones in the heart, brain, and testes of male rats with long-term, 7-month, streptozotocin T1DM and to assess the influence on them of 135-day therapy with intranasal insulin. It was shown that AC effects of β-adrenergic agonists in the heart, serotonin receptor agonists and PACAP-38 in the brain, chorionic gonadotropin and PACAP-38 in the testes, and somatostatin in all investigated tissues in long-term T1DM were drastically decreased. The treatment with intranasal insulin (0.48 IU/day) significantly restored these effects. The results were obtained suggesting that long-term T1DM induces significant alterations in hormone-sensitive AC system in the heart, brain, and testes that are much more pronounced, compared with short-term T1DM, and include a large number of hormonal regulations.

scholarly journals Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice

2019 ◽  
Vol 45 (2) ◽  
pp. 309-318 ◽  
Author(s):  
Sara Peñasco ◽  
Irantzu Rico-Barrio ◽  
Nagore Puente ◽  
Christine J. Fontaine ◽  
Almudena Ramos ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Ethanol Exposure ◽  
Long Term Depression ◽  
Cannabinoid Type 1 Receptor ◽  
Adult Mice

scholarly journals Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francisco J. Flores-Ramirez ◽  
Anapaula Themann ◽  
Jorge A. Sierra-Fonseca ◽  
Israel Garcia-Carachure ◽  
Samuel A. Castillo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Elevated Plus Maze ◽  
Later Life ◽  
Brain Regions ◽  
Fluoxetine Treatment ◽  
Trkb Receptors ◽  
Plus Maze ◽  
Bdnf Signaling ◽  
The Impact

AbstractThe objective of this study was to evaluate whether juvenile fluoxetine (FLX) exposure induces long-term changes in baseline responses to anxiety-inducing environments, and if so, whether its re-exposure in adulthood would ameliorate this anxiety-like phenotype. An additional goal was to assess the impact of adolescent FLX pretreatment, and its re-exposure in adulthood, on serotonin transporters (5-HTT) and brain-derived-neurotrophic-factor (BDNF)-related signaling markers (TrkB-ERK1/2-CREB-proBDNF-mBDNF) within the hippocampus and prefrontal cortex. To do this, female C57BL/6 mice were exposed to FLX in drinking water during postnatal-days (PD) 35–49. After a 21-day washout-period (PD70), mice were either euthanized (tissue collection) or evaluated on anxiety-related tests (open field, light/dark box, elevated plus-maze). Juvenile FLX history resulted in a persistent avoidance-like profile, along with decreases in BDNF-signaling markers, but not 5-HTTs or TrkB receptors, within both brain regions. Interestingly, FLX re-exposure in adulthood reversed the enduring FLX-induced anxiety-related responses across all behavioral tasks, while restoring ERK2-CREB-proBDNF markers to control levels and increasing mBDNF within the prefrontal cortex, but not the hippocampus. Collectively, these results indicate that adolescent FLX history mediates neurobehavioral adaptations that endure into adulthood, which are indicative of a generalized anxiety-like phenotype, and that this persistent effect is ameliorated by later-life FLX re-exposure, in a prefrontal cortex-specific manner.

Long-Term Outlook Improving for Type 1 Patients

2008 ◽  
Vol 38 (21) ◽  
pp. 14
Author(s):  
MIRIAM E. TUCKER

Evaluation of gastric emptying and neuropathy in short- and long-term type-1 diabetes

2006 ◽  
Vol 44 (05) ◽  
Author(s):  
T Várkonyi ◽  
É Börcsök ◽  
R Takács ◽  
R Róka ◽  
C Lengyel ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Short And Long Term ◽  
Term Type
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