Differential effects of estrogen and testosterone on auditory sensory gating in rats

• Published in: Psychopharmacology 2014-01, Vol.231 (1), p.243-256
• Main Authors: Thwaites, Shane J., van den Buuse, Maarten, Gogos, Andrea
• Format: Article
• Language: English
• Subjects: Amphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Apomorphine - pharmacology; Auditory Perception - drug effects; Biomedical and Life Sciences; Biomedicine; Body Weight - drug effects; Central Nervous System Stimulants - pharmacology; Complications and side effects; Dopamine Agonists - pharmacology; Dosage and administration; Drug therapy; Electrodes, Implanted; Electroencephalography; Electromyography; Estrogen; Estrogens; Estrogens - pharmacology; Evoked Potentials, Auditory - drug effects; Female; Male; Neurosciences; Orchiectomy; Organ Size - drug effects; Original Investigation; Ovariectomy; Pharmacology/Toxicology; Phencyclidine - pharmacology; Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Schizophrenia; Sensory Gating - drug effects; Sex Characteristics; Testosterone; Testosterone - pharmacology; Uterus - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3231-5

Rationale 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. Objectives 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.