Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories.

It is generally accepted that environmental enrichment enhances the performance and improves welfare of animals kept in captivity. Similar results have been obtained for fish. It has been previously reported that the presence of Blue or Red-Brown Substrate (BS and RBS respectively) on tank bottom resulted in growth enhancement and suppression of aggressive behavior of gilthead seabream Sparus aurata compared to Green Substrate (GS) and tanks without modifications (Control-C). In an attempt to identify the underlying mechanisms, in the present study the effects of this environmental enrichment on brain monoamine neurotransmitters and fatty acids of gilthead seabream were evaluated. BS and RBS fish had lower serotonergic activity (5-HIAA/5-HT), resulting mainly from lower 5-hydroxyindoleacetic acid (5-HIAA) levels. BS fish also had lower serotonin levels compared to all other treatments. Brain noradrenaline (NA) levels did not show significant differences between substrate treatments and control. Brain dopamine (DA) levels were lowest in BS and RBS fish, higher in GS fish and highest in C fish. No differences were observed for dopamine metabolites or dopaminergic activity. Moreover, brain NA was negatively correlated with body weight in BS fish and positively correlated in RBS and C fish. A positive correlation was also observed for brain DA with body weight in RBS fish. No differences were observed for brain fatty acids. Present results support the hypothesis that the beneficial effects of the presence of BS and RBS are related to altered social interactions and indicate the establishment of a less stressful social organization in enriched-reared fish groups.

Aromatase inhibitors block the conversion of androgens to oestrogens and are used for the treatment of hormone-responsive breast cancer in menopause and recently also in premenopausal women. We investigate whether decreased oestrogen synthesis following aromatase inhibition leads to a depressive-like behavioural response in cycling female rats. Using the forced swim test (FST) we estimate the response of acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine administration. Acute aromatase inhibition decreases immobility duration in the FST, indicating its antidepressant potential. Instead, sustained aromatase inhibition did not show such antidepressant potential. Testosterone elevation associates with the decreased depressive behaviour in the FST following acute letrozole treatment, but interestingly progesterone explains the increased swimming behaviour. Present findings may have potential implications for women treated with aromatase inhibitors, especially before menopause, as well as for the role of gonadal hormones in the expression of depressive symptoms and antidepressant response.

The presence of blue or red-brown substrate on the tank bottom has been previously reported as an efficient means of environmental enrichment for gilthead seabream. The present study aimed to investigate whether this enrichment is still beneficial when gilthead seabream is reared under different social conditions (i.e. a lower 4.9 kg m(-3) and a higher 9.7 kg m(-3) density). Water exchange was adjusted according to fish biomass to exclude density effects on water quality. In the enriched tanks single-colour glass gravel was used as substrate (blue and red-brown substrate, or BS and RBS respectively), while control tanks had no gravel. Growth, aggressive behaviour and size distribution results indicated that the lower density created a less favourable social environment. In both densities studied, BS enhanced growth, suppressed aggression and reduced brain serotonergic activity. In the condition of intense social interactions (i.e. the lower density) BS also reduced brain dopaminergic activity. These results along with the negative correlations observed between brain monoamines and fish body mass, indicated that substrate and density effects are socially-induced. However, there may be several biotic and/or abiotic factors interfering with substrate effects that should be investigated before the practical use of a substrate in land-based intensive aquaculture.