Estrogen treatment blocks 8-hydroxy-2-dipropylaminotetralin- and apomorphine-induced disruptions of prepulse inhibition: involvement of dopamine D1 or D2 or serotonin 5-HT1A, 5-HT2A, or 5-HT7 receptors.
Prepulse inhibition (PPI) is a measure of sensorimotor gating and an endophenotype of schizophrenia. We have shown previously in rats that estrogen treatment prevents disruption of PPI by the 5-HT(1A)/5-HT(7) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The aim of the present study was to examine the role of dopamine D(1) and D(2) and serotonin 5-HT(1A), 5-HT(2A), and 5-HT(7) receptors in these effects. Part 1 of this study investigated the ability of estrogen treatment to reverse PPI disruption induced by 8-OH-DPAT or the dopamine D(1)/D(2) receptor agonist apomorphine. Part 2 of this study compared 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, they received silastic implants containing either a low (E20) or high dose (E100) of estrogen. 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 pretreatment with the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg) and the typical antipsychotic and dopamine D(2) receptor antagonist haloperidol (0.25 mg/kg), but it was not reversed by pretreatment with the dopamine D(1) receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.1 mg/kg), the 5-HT(2A/2C) receptor antagonist ketanserin (2 mg/kg), or the 5-HT(7) 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 D(2) receptors downstream of 5-HT(1A) receptors.
Gogos
Andrea
A
Behavioral Neuroscience Laboratory, Mental Health Research Institute, 155 Oak St., Parkville (Melbourne), Victoria 3052, Australia.
Kwek
Perrin
P
Chavez
Carolina
C
van den Buuse
Maarten
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity*; D000818:Animals; D001058:Apomorphine / Q000633:toxicity*; D018491:Dopamine Agonists / Q000633:toxicity*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists / Q000633:toxicity*
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D004967:Estrogens; D044402:Receptor, Serotonin, 5-HT2A; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D004958:Estradiol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine