Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats

Gogos, Andrea; Buuse, Maarten van den

doi:10.1016/j.schres.2015.04.029

Cited by 29 publications

(23 citation statements)

References 58 publications

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“…Rodent studies provide clues regarding the underlying mechanisms of raloxifene action. In high doses, raloxifene, similar to oestrogen, is able to prevent reductions in PPI induced by the mixed dopamine D1/D2 receptor agonist apomorphine in ovariectomised adult female rats . In intact adult male rats, raloxifene treatment potentiates the effects of amphetamine by slowing the return to baseline locomotion levels .…”

Section: Evidence That Sex Steroid Manipulations Can Be Useful Adjuncmentioning

confidence: 97%

“…Treatment with oestrogen enhanced PPI in ovariectomised adult female rats and this effect was mimicked by testosterone; however, the effect of testosterone is more likely a result of its conversion to oestrogen because treatment with the non-aromatisable dihydrotestosterone had no effect on PPI. 44 Apomorphine-induced disruptions of PPI in ovariectomised adult female rodents can be prevented with oestrogen pretreatment, 45 suggesting a basis for inferring that inefficient oestrogen signalling may be involved in the manifestation of this phenotype in females with schizophrenia.…”

Section: Behavioural Studies On Prepulse Inhibition In Animalsmentioning

confidence: 99%

“…In high doses, raloxifene, similar to oestrogen, is able to prevent reductions in PPI induced by the mixed dopamine D1/D2 receptor agonist apomorphine in ovariectomised adult female rats. 45 In intact adult male rats, raloxifene treatment potentiates the effects of amphetamine by slowing the return to baseline locomotion levels. 113 These observations indicate a role for raloxifene in modulating dopaminergic-related molecules and are preliminary indications that this may be a mechanism through which raloxifene influences cognition and symptoms in schizophrenia patients.…”

Section: Selective Oestrogen Receptor Modulators (Serms): Raloxifenementioning

confidence: 99%

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Considering the role of adolescent sex steroids in schizophrenia

Owens

Murphy

Purves-Tyson

et al. 2018

J Neuroendocrinology

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Schizophrenia is a disabling illness that is typically first diagnosed during late adolescence to early adulthood. It has an unremitting course and is often treatment-resistant.Many clinical aspects of the illness suggest that sex steroid-nervous system interactions may contribute to the onset, course of symptoms and the cognitive impairment displayed by men and women with schizophrenia. Here, we discuss the actions of oestrogen and testosterone on the brain during adolescent development and in schizophrenia from the perspective of experimental studies in animals, human post-mortem studies, magnetic resonance imaging studies in living humans and clinical trials of sex steroid-based treatments. We present evidence of potential beneficial, as well as detrimental, effects of both testosterone and oestrogen. We provide a rationale for the necessity to further elucidate sex steroid mechanisms of action at different ages, sexes and brain regions to more fully understand the role of testosterone and oestrogen in the pathophysiology of schizophrenia. The weight of the evidence suggests that sex steroid hormones influence mammalian brain function, including both cognition and emotion, and that pharmaceutical agents aimed at sex steroid receptors appear to provide a novel treatment avenue to reduce symptoms and improve cognition in men and women with schizophrenia.

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Section: Evidence That Sex Steroid Manipulations Can Be Useful Adjuncmentioning

confidence: 97%

Section: Behavioural Studies On Prepulse Inhibition In Animalsmentioning

confidence: 99%

Section: Selective Oestrogen Receptor Modulators (Serms): Raloxifenementioning

confidence: 99%

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Considering the role of adolescent sex steroids in schizophrenia

Owens

Murphy

Purves-Tyson

et al. 2018

J Neuroendocrinology

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“…PPI is the attenuation of the acoustic startle response to an intense audiogenic stimulus (pulse) by a preceding, weaker acoustic stimulus (prepulse). PPI is used as an operational measure of sensorimotor gating, a process which is deficient in schizophrenia, and can be measured with analogous methods in rodents [28][29][30].We and others have previously investigated the effects of ovariectomy, ovarian hormones, and their synthetic analogues in PPI [31][32][33][34][35]. For example, while ovariectomy had no effect on PPI [31-33], treatment with the estrogen, 17β-estradiol, could reverse PPI deficits that were induced by serotonin 1A (5-HT 1A ) receptor agonists in both female rats [32] and healthy women [36].…”

mentioning

confidence: 99%

“…We and others have previously investigated the effects of ovariectomy, ovarian hormones, and their synthetic analogues in PPI [31][32][33][34][35]. For example, while ovariectomy had no effect on PPI [31-33], treatment with the estrogen, 17β-estradiol, could reverse PPI deficits that were induced by serotonin 1A (5-HT 1A ) receptor agonists in both female rats [32] and healthy women [36].…”

mentioning

confidence: 99%

The Impact of Removal of Ovarian Hormones on Cholinergic Muscarinic Receptors: Examining Prepulse Inhibition and Receptor Binding

et al. 2020

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Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [ 3 H]-pirenzepine, [ 3 H]-AF-DX, and [ 3 H]-4-DAMP, to label M 1 , M 2 /M 4 , and M 3 receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density.Brain Sci. 2020, 10, 106 2 of 12 onset of schizophrenia in men [5]; the latter phenomenon is consistent across cultures and independent of the diagnostic classification system used [6][7][8]. There is also evidence to suggest that the impact of ovarian hormones on the symptoms of schizophrenia varies across the reproductive lifespan of women, which is underscored by changing levels of hormones, including the main ovarian hormones, estrogen and progesterone [8][9][10]. Overall, these factors lead to a less severe course of illness, milder symptoms, and superior treatment outcomes in women.Cholinergic signaling plays a crucial role in multiple cognitive processes, including learning, memory, and sensory perception [11]. Converging lines of evidence have implicated muscarinic cholinergic signaling in the pathophysiology of schizophrenia. In patients with schizophrenia, in vivo muscarinic receptor availability was reduced [12,13], and postmortem radioligand binding studies using [ 3 H]-pirenzepine, which label muscarinic M 1 and M 4 receptors, have indicated that the densities of these receptors were decreased in the prefrontal cortex, anterior cingulate cortex, hippocampus, and caudate putamen of schizophrenia patients [14][15][16][17][18]. Notably, decreased levels of both M 1 mRNA levels [17,19,20] and M 1 receptor protein, but not M 2 , M 3 , or M 4 receptor protein [17,21], were observed in the dorsolateral prefrontal cortex and superior prefrontal gyrus from people with schizophrenia. These data suggest that low levels of cortical M 1 receptors are a significant c...

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