Effects of antipsychotics and selective D3 antagonists on PPI deficits induced by PD 128907 and apomorphine.
Rats treated with apomorphine and amphetamine display sensorimotor gating impairments, as measured by prepulse inhibition (PPI), and these impairments can be reversed by antipsychotic treatment. However, it remains unknown whether the dopamine (DA) D(3) receptor plays a role in mediating these effects on PPI, as none of these DA agonists or antipsychotics are exclusively selective at either D(2) or D(3) receptors. To address this question, the current study was designed to investigate whether antipsychotic drugs and selective D(3) antagonists could block the PPI-disruptive effects of PD 128907 (a preferential D(3) agonist) and apomorphine. We found that the effect of PD 128907 on PPI in rats could be antagonized by risperidone, clozapine, and the selective D(3) antagonists SB 277011 and A-691990, but not by raclopride or haloperidol, while the apomorphine-induced PPI deficit could be reversed by risperidone, clozapine and haloperidol, but not by SB 2770111 and A-691990. These results suggest that the D(3) receptor does not mediate apomorphine-induced disruption of PPI in rats, however, given the findings that PD 128907 elicited a PPI-disruptive effect that was blocked by selective D(3) antagonists, a role of D(3) receptor in mediating PPI in rats cannot be ruled out. The possible mechanisms of D(3) receptor involvement in PPI are discussed.
Zhang
Min
M
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. min.zhang@abbott.com
Ballard
Michael E
ME
Unger
Liliane V
LV
Haupt
Andreas
A
Gross
Gerhard
G
Decker
Michael W
MW
Drescher
Karla U
KU
Rueter
Lynne E
LE
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007266:Inhibition, Psychological; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D014150:Antipsychotic Agents; D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009570:Nitriles; D010078:Oxazines; C409982:SB 277011; D044005:Tetrahydroisoquinolines; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D001058:Apomorphine