Abstract
The aim of the present study was to investigate the effect of estrogen and progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT1A) receptor-mediated disruption of prepulse inhibition (PPI) of acoustic startle. The age-at-onset of schizophrenia is later in women than men, and it has been suggested that women may be protected from schizophrenia by the sex steroid hormone estrogen. 5-HT1A receptors have been implicated in the development of schizophrenia and the action of antipsychotics. PPI is a model of sensorimotor gating that is deficient in schizophrenia and other illnesses. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with a low dose of estrogen (E20), a high dose of estrogen (E100), progesterone (P), or both the E20- and P-filled (E/P) silastic implants. Two weeks later, the rats were randomly treated with saline, or 0.02 or 0.5 mg/kg of the 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). Treatment with 8-OH-DPAT resulted in a dose-dependent increase in startle amplitude in all rat groups. PPI was significantly reduced after injection of 0.5 mg/kg 8-OH-DPAT in sham-operated rats, untreated OVX rats, E20-treated OVX rats, and P-treated OVX rats. In contrast, in E100- and E/P-treated OVX rats, PPI was not significantly reduced by 0.5 mg/kg 8-OH-DPAT. These data suggest that treatment with a high dose of estrogen, or with a combination of estrogen and progesterone, prevents 8-OH-DPAT-induced disruption of PPI. Thus, these hormones could be protective against sensorimotor gating deficits, at least those induced by 5-HT1A receptor stimulation, and may therefore be beneficial against some symptoms of schizophrenia.
Footnotes
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This study was supported by The Jack Brockhoff Foundation and the National Health and Medical Research Council of Australia. This work was previously presented: Gogos A and Van den Buuse M (2003) Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1A receptor agonist 8-OH-DPAT. Proc Aust Neurosci Soc14:Oral-10-01.
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DOI: 10.1124/jpet.103.061432.
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ABBREVIATIONS: D, dopamine; 5-HT, 5-hydroxytryptamine (serotonin); PPI, prepulse inhibition; P, progesterone; OVX, ovariectomized; E20, 20% 17β-estradiol; E100, 100% 17β-estradiol; E/P, 20% 17β-estradiol and progesterone; 8-OH-DPAT, 8-hydroxy-2-dipropylaminotetralin; ANOVA, analysis of variance; PP, prepulse; WAY 100,135, N-tert-butyl-3[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpropanamide.
- Received October 10, 2003.
- Accepted December 22, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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Estrogen and Progesterone Prevent Disruption of Prepulse Inhibition by the Serotonin-1A Receptor Agonist 8-Hydroxy-2-dipropylaminotetralin
