Desinhibitory effect of allopregnanolone within the medial prefrontal cortex of male rats on the lus maze test.

CASTELLER, G.; FRAILE, M.; LACONI, M.; LANDA, A.I.; CABRERA, R.; GARGIULO, P.A.

International Journal of Neuroprotection and Neuroregeneration

RPA Publications

Año: 2006 vol. 2 p. 120 - 126

1745-1183

Casteller, G.; Fraile, M.; Laconi, M.; Landa, A.I.; Cabrera, R.; Gargiulo, P.A.  International Journal of Neuroprotection and Neuroregeneration (2006) 2: 120-126. Objectives: The aim of the present paper is to study the behavioural effects of Allopregnanolone (ALLO), a neurosteroid derived from progesterone, on performance in the plus maze test. It was studied in male rats injected into the medial prefrontal cortex (mPFC).  Methodology: The rats, bilaterally cannulated into the mPFC, were divided into 3 groups and received either injections of vehicle, or ALLO (0.06 and 0.6 mM solution) 30 min before testing. Time spent in open arm, time spent in the distal extreme, time per entry, total arm entries, preference index, open arm entries and closed arm entries were recorded. Results: Time spent in the open arm was increased with both doses of ALLO (p<0.001), and in the same way time spent in the distal extreme (p<0.001). Time per entry was not modified by treatment. Total arm entries were increased by the lower dose of ALLO (p<0.001) but not by the higher, and preference index was clearly increased by both doses (p<0.01). Open arm entries were increased by both doses when compared with controls (p<0.001), and statistical differences were observed when the lower and the higher doses were compared (p<0.05). No differencs were seen in closed arm entries. Conclusion: We conclude that ALLO injection within mPFC induces a desinhibitory action, with some similarities, but also differences, with an anxiolytic-like effect. This experimental approach could be globally considered as a model of schizophrenic behavioral desinhibition related to affective flattening. Furthermore, it gives additional evidences in the way of understanding epidemiological facts, like the age of presentation of schizophrenia after puberty, and strongly suggests a possible role for neurosteroids in the initial schizophrenic syndrome.  KEY WORDS: Allopregnanolone, medial prefrontal cortex, anxiety, plus-maze, schizophrenia, affective flattening.