LVR-Klinikum Düsseldorf Hospital of the Heinrich-Heine University ...

specific anxiety behaviour and associated alterations in
exploration behaviour, as well as aspects of social behaviour.
Morphological changes of hippocampal pyramidal cells
and histochemical parameters such as the activity of
acetylcholine esterase and cytochrome-c-oxidase were also
investigated. After sexual maturation, the animal model
of prenatal damage established by our group led to sexspecific
alterations in weight, behaviour (anxiety and social
behaviour, learning and memory functions) and the length
of hippocampal pyramidal cells, findings comparable with
symptoms of individuals with schizophrenia.
Influence of selected antipsychotic drugs on serum
leptin levels and the distribution of leptin receptors in
the hypothalamus of rats
Project period: 2003–2006
Financing: Departmental research budget
Food intake, energy consumption and the closely associated
long-term regulation of body weight are physiological
control mechanisms which are partly located in the brain
and partly in peripheral tissues. Here, leptin plays a key role,
since it signals body fat mass to the brain and regulates
the secretion of neuropeptides mediated by hippocampal
leptin receptors. The treatment of patients with mental
disorders with antipsychotic drugs may lead to a range
of unwanted side effects. Particularly in treatment with
atypical antipsychotic drugs, some individuals gain so
much weight that, in the worst cases, medication may
have to be discontinued. Overweight may lead to serious
cardiovascular, respiratory and gastrointestinal disorders.
Typical and atypical antipsychotic drugs were administered
in a feeding experiment to three-month-old rats, to avoid the
hormonal effects of puberty. Body weight, daily food intake
and drinking behaviour were investigated over a period
of six weeks. Serum and cardial blood leptin levels were
determined. The distribution of the leptin receptor in the
hypothalamus was determined immunochemically by using
electrophoresis and Western Blot. It could be demonstrated
that typical (haloperidol) and atypical (clozapine and
ziprasidone) antipsychotic drugs have no effect on the leptin
level in the serum or the expression of the leptin receptor in
the hypothalamus.
Mean value ± SEM (length in mm)
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86
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Control right
Control left
Treated rats right
Treated rats left
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Male Female
ReseaRch
Figure 11: After prenatal damage by neurotoxic kainic acid, which was
injected into the third ventricle of the brain, rats show sex-specific changes
in the length of the pyramidal cells. This tallies with post-mortem findings
in patients suffering from schizophrenia (figure modified after: v Wilmsdorff
M, Sprick U,Bouvier ML, Schulz D, Schmitt A, Gaebel W: Sex-dependent
behavioral effects and morphological changes in the hippocampus after
prenatal invasive interventions in rats: implications for animal models of
schizophrenia. Clinics. 2010; 65(2): 209–219)
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Preparation of brain sections (rats) for microscopic investigation
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