Repeated and chronic administration of Vardenafil or Sildenafil differentially affects emotional and socio-sexual behavior in mice.

Selective phosphodiesterases (PDEs) inhibitors have been widely studied as therapeutic agents for treatment of various human diseases, including cardiotonics, vasodilators, smooth muscle relaxants, antidepressants, antithrombotics, antiasthmatics, and agents for improving learning and memory. Although Sildenafil(®) and Vardenafil(®) have similar chemical formulae, the same target and interact with many of the same residues at the active site of phosphodiesterse-5 (PDE-5), they exhibit both in vitro and in vivo some important functional differences that could differentially affect behavior. Therefore we assessed whether repeated and chronic administration of Vardenafil and Sildenafil at a dose based upon human treatment can differentially affect aggressive, social, emotional and sexual behavior. To this aim, the effects of Sildenafil (10mg/kg) or Vardenafil (2mg/kg) (t.i.w., for 5 weeks) were observed in CD1 subordinate male mice in a low aggression and social subordination context. The results show that Sildenafil increased competitive aggression, environmental and social exploration, and reduced anxiety like behaviors as compared to controls, whereas Vardenafil had a significant major effect on appetitive and consummatory aspect of sexual behavior. This demonstrates that Sildenafil and Vardenafil, although being structurally and functionally similar, are characterized by different neuro-behavioral actions and can have differential therapeutic potentials.

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens.

Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999-1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attention-deficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

Cross fostering in mice: behavioral and physiological carry-over effects in adulthood.

Cross fostering is a widely used laboratory practice. However, relatively few studies have directly investigated the carry-over effects of this procedure in adult animals. The aim of the present study is to investigate the late effects of cross fostering (CF) at birth (in litters composed of no siblings) on adult mice. When adults, cross-fostered male and female mice were examined for intrasex aggression, and levels of emotionality, exploration and anxiety. In addition, body weight was monitored, several internal organs were weighed and plasma corticosterone levels were measured. When compared to controls, body weight of CF male and female mice was increased, at least after early puberty. CF males showed smaller preputial glands, while basal corticosterone level was not affected by cross fostering. In the free-exploratory test, CF males, but not females, showed a behavioral profile suggestive of lower anxiety. These effects in adulthood cannot be ascribed to differences in the maternal care received, which was not affected by cross fostering. In conclusion, cross fostering at birth induced a number of behavioral and physiological alterations in mice, particularly in males. These findings should be carefully evaluated when applying cross fostering procedure to laboratory animals.

Social stress in mice: gender differences and effects of estrous cycle and social dominance.

A large discrepancy in the possibility of inducing social stress in the two genders exists. Since generalizations of findings from one sex to the other appear not to be valid, reliable models of social stress in females are needed. We examined the effects of social context in the housing environment, as a possible source of stress, on exploration and anxiety in male and female mice, taking into account the estrous phase for females and the social status for males as additional variables. Mice housed individually or with siblings were tested in a free-exploratory paradigm of anxiety (where test animals have a choice to stay in their home cage or to explore an open field, OF). Individually housed females did not leave their home cage for long periods, explored less the unfamiliar area and displayed higher risk assessment, a behavioral profile suggestive of lower propensity for exploration and higher level of anxiety compared with group-housed females. Individually housed males tended to show an opposite profile. Proestrus mice were less sensitive to the decrease of exploratory propensity induced by individually housing compared to estrus and diestrus mice. Social dominants and social subordinates in sibling groups did not differ in their exploratory responses to the OF. Different housing procedures, as means to provide different social environment, may differentially induce mild social stress in male and female mice.