PT  - JOURNAL ARTICLE
AU  - Andrea Gogos
AU  - Perrin Kwek
AU  - Carolina A Chavez
AU  - Maarten van den Buuse
TI  - Estrogen treatment blocks 8-OH-DPAT- and apomorphine-induced disruptions of prepulse inhibition: involvement of dopamine D<sub>1</sub> or D<sub>2</sub>, serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub> or 5-HT<sub>7</sub> receptors
AID  - 10.1124/jpet.109.162123
DP  - 2009 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.109.162123
4099  - http://jpet.aspetjournals.org/content/early/2009/12/30/jpet.109.162123.short
4100  - http://jpet.aspetjournals.org/content/early/2009/12/30/jpet.109.162123.full
AB  - Prepulse inhibition (PPI) is a measure of sensorimotor gating and an endophenotype of schizophrenia. We have previously shown that estrogen treatment prevents disruption of PPI by the 5-HT1A/5-HT7 receptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT). The aim of the present study was to examine the role of dopamine D1 and D2, 5-HT1A, 5-HT2A and 5-HT7 receptors in these effects. Part 1 of this study investigated the ability of estrogen treatment to reverse a PPI disruption induced by 8-OH-DPAT or the dopamine D1/D2 receptor agonist, apomorphine. Part 2 of this study aimed to compare these effects to the ability of various antagonists in reversing the action of 8-OH-DPAT and apomorphine on PPI. Female Sprague-Dawley rats were ovariectomized (OVX) and, where appropriate, received silastic implants containing either a low- (E20) or high-dose of estrogen (E100). Two weeks later, PPI was assessed using automated startle boxes. The disruption of PPI by either treatment with 8-OH-DPAT (0.5 mg/kg) or apomorphine (0.3 mg/kg) was similarly prevented by E100 treatment. 8-OH-DPAT-induced PPI disruption was reversed by pre-treatment with the 5-HT1A receptor antagonist, WAY 100,635 (1 mg/kg) and the typical antipsychotic and dopamine D2 receptor antagonist, haloperidol (0.25 mg/kg), but not the dopamine D1 receptor antagonist, SCH 23390 (0.1 mg/kg), 5 HT2A/2C receptor antagonist, ketanserin (2 mg/kg) or 5-HT7 receptor antagonist, SB-269970 (10 mg/kg). Apomorphine-induced disruptions of PPI were reversed by haloperidol and SCH 23390 only. Estrogen may prevent disruptions of PPI induced by both 8-OH-DPAT and apomorphine, by an action on dopamine D2 receptors downstream of 5-HT1A receptors.The American Society for Pharmacology and Experimental Therapeutics