Differential effects of estrogen and testosterone on auditory sensory gating in rats.
BACKGROUND
Estrogen has been shown to have beneficial effects in patients with schizophrenia. However, the mechanisms involved in this protective effect are unclear. Schizophrenia is associated with deficits in sensory gating, a filtering mechanism which normally prevents sensory overload. In rodent models, acute treatment with drugs such as the dopamine D1/D2 receptor agonist, apomorphine; the dopamine releaser, amphetamine; and the glutamate NMDA receptor antagonists, phencyclidine or MK-801, can induce a phenotype similar to that seen in schizophrenia.


OBJECTIVE
Given the putative protective action of estrogen in schizophrenia, here we investigated the effect of ovariectomy (OVX) and estrogen replacement in female rats on drug-induced auditory gating deficits. For comparison, we also assessed the effects of castration (CAST) and dihydrotestosterone (DHT) replacement in male rats.


METHODS
Rats were instrumented with cortical surface electrodes. Test sessions comprised of 150 presentations of paired clicks, 500 ms apart (S1 and S2).


RESULTS
Administration of all drugs increased the ratio of responses to S2/S1 in sham-operated female and male rats. OVX reduced event-related potential amplitudes but did not alter S2/S1 ratio or drug effects. In OVX rats with 17β-estradiol implants, the effect of apomorphine was abolished, but there was no change in that of amphetamine and phencyclidine. There were no effects of CAST or DHT replacement in male rats.


CONCLUSIONS
Chronic estrogen replacement in OVX rats protected against sensory gating deficits caused by direct dopamine D1/D2 receptor stimulation. These data could indicate a possible mechanism by which estrogen exerts a protective action in schizophrenia.
Behavioural Neuroscience Laboratory, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
Shane J
SJ
Thwaites
Maarten
M
van den Buuse
Andrea
A
Gogos
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001307:Auditory Perception / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004576:Electromyography; D004967:Estrogens / Q000494:pharmacology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects*; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D004967:Estrogens; D013739:Testosterone; D000661:Amphetamine; D010622:Phencyclidine; D001058:Apomorphine