Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats.

Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors.

Cell sex determines anoikis resistance in vascular smooth muscle cells.

Sexual dimorphism, detectable in vascular smooth muscle cells freshly isolated from aorta of male and female rats, is associated with a different susceptibility to radiation-induced apoptosis. In this work we investigated the mechanism underlying this difference and discovered that, in comparison with cells from male rats, cells from female rats show adhesion-associated resistance to apoptosis, the so called anoikis resistance. This is apparently due to a more adhering phenotype, characterized by a well organized actin microfilament cytoskeleton and to an increased phosphorylated focal adhesion kinase, and, more importantly, to a higher propensity to undergo survival by autophagy.

Cell sex: a new look at cell fate studies.

Cell death processes have been widely investigated in recent years in order to elucidate the different pathways involved in the complex machinery implicated in determining cell fate. Different forms of cell death have been described: Apart from the classical form of death known as necrosis, a well-characterized traumatic injury of the cell, several additional forms of cell death have been identified. Of these, apoptosis has been characterized in the greatest detail. Defects in the mechanisms of cell demise (that is, an excess of or decrease in apoptosis) have been associated with the pathogenesis of a number of human diseases. Here we review some new aspects derived from recent insights into this field, particularly the hypothesis that cells of males and females could display several different features, including those determining their fate.

Redox state and gender differences in vascular smooth muscle cells.

Vascular smooth muscle cells (VSMC) have been isolated from male and female rat aorta and studied to assess their susceptibility to ultraviolet radiation-induced oxidative stress. Interestingly, a gender difference, in terms of reactive oxygen species production, was detected in both basal and irradiated VSMC. Namely, VSMC from male rats were more susceptible to radiation-induced stress and easier underwent apoptosis in comparison to cells from female rats. Conversely, the latter, in the same experimental conditions, clearly displayed signs of premature senescence. These results indicate that a sort of "gender memory" can be conserved in VMSC in primary culture.

Are the available experimental models of type 2 diabetes appropriate for a gender perspective?

Several experimental models have so far been developed to improve our knowledge of the pathogenetic mechanisms of type 2 diabetes mellitus (T2D), to determine the possible pharmacological targets of this disease and to better evaluate diabetes-associated complications, e.g. the cardiovascular disease. In particular, the study of T2D gained the attention of several groups working with different animal species: rodents, cats or pigs, as well as other non-human primate species. Each of these species provided useful and different clues. However, T2D has to be considered as a gender-associated disease: sex differences play in fact a key role in the onset as well as in the progression of the disease and a higher mortality for cardiovascular diseases is detected in diabetic women with respect to men. The results obtained from all the available animal models appear to only partially address this issue so that the search for more precise information in this respect appears to be mandatory. In this review we summarize these concepts and literature in the field and propose a reappraisal of the various animal models for a study of T2D that would take into consideration a gender perspective.