Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats.
Prepulse inhibition (PPI) of the startle reflex is reduced by systemic administration of dopamine (DA) agonists. Since PPI is impaired in patients with schizophrenia, the DA agonist-induced disruption of PPI in rats may be a useful model for studying the pathophysiology of impaired sensorimotor gating in schizophrenia. In the present study, we replicated the observation that PPI is disrupted by systemic administration of the D2 agonist quinpirole, but not by the D1 agonist SKF 38393. PPI caused by weak [1-5 dB(A)] or more intense [10 dB(A)] prepulses was also disrupted by quinpirole infusion into the nucleus accumbens (NAC). The effects of intraaccumbens quinpirole on PPI were blocked by pretreatment with the D2 antagonist haloperidol. These results support the notion that the reduction of PPI after systemic administration of DA agonists is mediated via stimulation of NAC D2 receptors.
Wan
F J
FJ
Department of Neuroscience and Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804.
Swerdlow
N R
NR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol