Sex-dependent behavioral effects and morphological changes in the hippocampus after prenatal invasive interventions in rats: implications for animal models of schizophrenia.
OBJECTIVE
Although schizophrenia affects both human genders, there are gender-dependent differences with respect to age of onset, clinical characteristics, course and prognosis of the disease.


METHODS
To investigate sex-dependent differences in motor coordination and activity as well as in cognitive and social behavior, we repeatedly tested female (n = 14) and male (n = 12) Fisher rats (postnatal days, PD 56-174) that had received intracerebroventricular injections of kainic acid as well as female (n = 15) and male (n = 16) control animals. The hippocampus was examined histologically.


RESULTS
Compared to male controls, in the alcove test both female controls and female animals with prenatal intervention spent less time in a dark box before entering an unknown illuminated area. Again, animals that received prenatal injection (particularly females) made more perseveration errors in the T-maze alternation task compared to controls. Female rats exhibited a higher degree of activity than males, suggesting these effects to be sex-dependent. Finally, animals that received prenatal intervention maintained longer lasting social contacts. Histological analyses showed pyramidal cells in the hippocampal area CA3 (in both hemispheres) of control animals to be longer than those found in treated animals. Sex-dependent differences were found in the left hippocampi of control animals and animals after prenatal intervention.


CONCLUSIONS
These results demonstrate important differences between males and females in terms of weight gain, response to fear, working memory and social behavior. We also found sex-dependent differences in the lengths of hippocampal neurons. Further studies on larger sample sets with more detailed analyses of morphological changes are required to confirm our data.
von Wilmsdorff
Martina
M
LVR-Klinikum Düsseldorf, Kliniken der Heinrich-Heine-Universität - Düs-seldorf/Germany. martina.wilmsdorff@lvr.de
Sprick
Ulrich
U
Bouvier
Marie-Luise
ML
Schulz
Daniela
D
Schmitt
Andrea
A
Gaebel
Wolfgang
W
D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D007276:Injections, Intraventricular; D007608:Kainic Acid; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology*; D012737:Sex Factors; D012919:Social Behavior
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid