@article {Gogos267, author = {Andrea Gogos and Maarten Van den Buuse}, title = {Estrogen and Progesterone Prevent Disruption of Prepulse Inhibition by the Serotonin-1A Receptor Agonist 8-Hydroxy-2-dipropylaminotetralin}, volume = {309}, number = {1}, pages = {267--274}, year = {2004}, doi = {10.1124/jpet.103.061432}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/309/1/267}, eprint = {https://jpet.aspetjournals.org/content/309/1/267.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }