Selective enhancement of NMDA receptor-mediated locomotor hyperactivity by male sex hormones in mice

van den Buuse, Maarten, Low, Jac kee, Kwek, Perrin, Martin, Sally, and Gogos, Andrea (2017) Selective enhancement of NMDA receptor-mediated locomotor hyperactivity by male sex hormones in mice. Psychopharmacology, 234 (18). pp. 2727-2735.

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Altered glutamate NMDA receptor function is implicated in schizophrenia, and gender differences have been demonstrated in this illness.

This study aimed to investigate the interaction of gonadal hormones with NMDA receptor-mediated locomotor hyperactivity and PPI disruption in mice.

The effect of 0.25 mg/kg of MK-801 on locomotor activity was greater in male mice than in female mice. Gonadectomy (by surgical castration) significantly reduced MK-801-induced hyperlocomotion in male mice, but no effect of gonadectomy was seen in female mice or on amphetamine-induced locomotor hyperactivity. The effect of MK-801 on prepulse inhibition of startle (PPI) was similar in intact and castrated male mice and in ovariectomized (OVX) female mice. In contrast, there was no effect of MK-801 on PPI in intact female mice. Forebrain NMDA receptor density, as measured with [H-3]MK-801 autoradiography, was significantly higher in male than in female mice but was not significantly altered by either castration or OVX.

These results suggest that male sex hormones enhance the effect of NMDA receptor blockade on psychosis-like behaviour. This interaction was not seen in female mice and was independent of NMDA receptor density in the forebrain. Male sex hormones may be involved in psychosis by an interaction with NMDA receptor hypofunction.

Item ID: 50698
Item Type: Article (Research - C1)
ISSN: 1432-2072
Keywords: NMDA receptor, sex hormones, testosterone, schizophrenia
Funders: National Health and Medical Research Council (NHMRC), Victorian State Government
Date Deposited: 20 Sep 2017 11:06
FoR Codes: 42 HEALTH SCIENCES > 4203 Health services and systems > 420313 Mental health services @ 20%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320599 Medical biochemistry and metabolomics not elsewhere classified @ 80%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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