Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1A receptor agonist 8-hydroxy-2-dipropylaminotetralin.
The aim of the present study was to investigate the effect of estrogen and progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT(1A)) 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-HT(1A) 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-HT(1A) 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-HT(1A) receptor stimulation, and may therefore be beneficial against some symptoms of schizophrenia.
Gogos
Andrea
A
Behavioral Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia.
Van den Buuse
Maarten
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D009433:Neural Inhibition / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D004967:Estrogens; D017366:Serotonin Receptor Agonists; D011374:Progesterone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin