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No / Sexual dysfunction is a major, although poorly understood, side-effect of treatment with antipsychotic drugs. We have recently show marked disruption of reproductive function and weight gain in female rats treated subchronically with risperidone and haloperidol. The aim of the present study was to examine further the potential relationship between reproductive dysfunction and weight gain in female rats treated with olanzapine. The effects of olanzapine on weight gain, food and water intake, intra-abdominal fat, the oestrous cycle and uterine weight were assessed in group-housed adult female hooded-Lister rats. Olanzapine (0.5-4.0 mg/kg i.p.) or vehicle was administered once daily for 21 days and body weight, food and water intake measured, with histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 22, animals were sacrificed and intra-abdominal fat, wet and dry uterine weights measured. Olanzapine induced significant weight gain with concomitant increases in food and water intake and intra-abdominal fat without an effect on the oestrous cycle, wet and dry uterine weights or plasma prolactin levels. These results confirm the ability of olanzapine to induce weight gain in female rats on unrestricted normal diet with a concomitant increase in food and water intake and increased intra-abdominal fat. These effects of olanzapine were produced in the absence of any apparent impairment in reproductive function, in contrast to the substantial disruption of oestrous and uterine atrophy previously shown in rats treated with risperidone and haloperidol.

No / Rationale: Weight gain caused by some antipsychotics is not only confined to adults but can also adversely affect both children and adolescents. Indeed, olanzapine and risperidone have been associated with extreme weight gain in adolescents even greater than that reported in adults. We have recently shown substantial weight gain in adult female rats following treatment with olanzapine and risperidone but not ziprasidone. Objectives: The aim of the present study was to compare the effects of several antipsychotics on weight gain and reproductive function in juvenile (aged 7 weeks) female hooded Lister rats. Methods: Olanzapine (4 mg/kg), risperidone (0.5 mg/kg), ziprasidone (2.5 mg/kg), sulpiride (10 mg/kg), haloperidol (0.5 mg/kg) or vehicle was administered i.p. once per day for 21 days. Body weight, food and water intake were measured daily, in addition to the determination of stage of the oestrous cycle. Results: Sub-chronic administration of olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone, significantly increased body weight compared to vehicle-treated animals during weeks 1-3. Sulpiride significantly increased food and water intake. Significantly increased percentage intra-abdominal fat weight was observed in olanzapine, risperidone, sulpiride and haloperidol, but not ziprasidone-treated animals. Marked disruption of the oestrous cycle was observed in all but the ziprasidone-treated group, which continued to have regular 4-day oestrous cycles. Conclusions: Weight gain observed in these juvenile animals was 1.5-2 times greater than that previously observed in adult rats. These findings have important implications for the use of antipsychotics in children and adolescent patients.

Yes / Long-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12h:12h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling. / BBSRC (grant number BB/K001043/1) and the Scottish Government.

Yes / In this study the effects of photoperiod and diet, and their interaction, were examined for their effects on growth and body composition in juvenile F344 rats over a 4-week period. On long (16L:8D), relative to short (8L:16D), photoperiod food intake and growth rate were increased, but percentage adiposity remained constant (ca 3-4%). On a high fat diet (HFD), containing 22.8% fat (45% energy as fat), food intake was reduced, but energy intake increased on both photoperiods. This led to a small increase in adiposity (up to 10%) without overt change in body weight. These changes were also reflected in plasma leptin and lipid levels. Importantly while both lean and adipose tissue were strongly regulated by photoperiod on a chow diet, this regulation was lost for adipose, but not lean tissue, on HFD. This implies that a primary effect of photoperiod is the regulation of growth and lean mass accretion. Consistent with this both hypothalamic GHRH gene expression and serum IGF-1 levels were photoperiod dependent. As for other animals and humans, there was evidence of central hyposomatotropism in response to obesity, as GHRH gene expression was suppressed by the HFD. Gene expression of hypothalamic AgRP and CRH, but not NPY nor POMC, accorded with the energy balance status on long and short photoperiod. However, there was a general dissociation between plasma leptin levels and expression of these hypothalamic energy balance genes. Similarly there was no interaction between the HFD and photoperiod at the level of the genes involved in thyroid hormone metabolism (Dio2, Dio3, TSHβ or NMU), which are important mediators of the photoperiodic response. These data suggest that photoperiod and HFD influence body weight and body composition through independent mechanisms but in each case the role of the hypothalamic energy balance genes is not predictable based on their known function. / Scottish Government (Rural and Environment Science and Analytical Services Division, http://www.scotland.gov.uk/), AWR LR LMT PJM and the BBSRC, (http://www.bbsrc.ac.uk/home/home.aspx, grant BB/K001043/1), AWR GH PJM

This theses deals with the storage length of artificially spawn of hard roes of Tench (Tinca tinca) during different temperatures at the time before the semen discharging and activation to fertilization, hatching and consequent survival of fish hatchery throughout changeover from the embryonic to larval life period (beginning of active food intake). Homogeneous assortment of hard roes obtained from hormonally induced artificial hatching of 6 spawners has been used for this experiment. Samples of hard roes were put into plastic bowls and covered, immediately after artificial hatching. Subsequently, they were placed into tempered, thermo-isolating containers with temperatures of 5, 10, 15, 20, 25 and 30 °C. In time intervals of 0.5; 1; 1,5; 2; 3; 4; 6; 8 and 10 hours, a small amount of hard roes were taken away from each temperature (estimated 50 -100 pieces) and put into dry, glass beakers (in 3 repetitions in each temperature combination and length of storage). Subsequently, the semen discharging from 6 milters was carried out and activation by water was performed. Incubation took place in non-sticking environment. During the incubation, or more precisely during the consequent storage of embryos through temperatures between 19-20.5 °C, water was changed daily. Fertilization was evaluated 48 hours after fertilizing. Hatchery was determined 48 hours after beginning of hatching of first specimen. After changeover from embryonic to larval period of ontogenetic development, living food was offered to hatching fish (artemia sp.). Thereafter, the amount of hatched fish with filled intestines was counted. Ascertained values were depicted as a percentage from the total number of seeded hard roes as well as fertilized hard roes with the use of statistic methods (two factors Anovy with the repetition). The highest level (in statistic evaluation on the importance level alfa = 0.05) of hard roe hatchery was accomplished throughout the length of possession and temperature 1 hour/ 25 °C (68.0 +- 3.1 %). The high level of hatchery was maintained by hard roes stored for 2 hours, afterwards a gradual value decrease was registered. Similarly, that was achieved with hatching parameter, where the high level of hatching was achieved with hard roes possessed for the period of 3 hours (except temperature of 30 °C), afterwards the hatchery was decreased. Pursued survival and food intake parameters of hatched fish (from the practical point of view) confirmed above stated dispositions. The high hatchery from placed hard roes was maintained for 1.5 - 3 hours (except 30 °C), thereafter there was its gradual decrease. In the time of 8 hours (temperatures 5 - 20 °C), the survival of 1.2 +- 1.8 %, was found out, with the rest, the survival was nearly zero.