Reduced startle gating after D1 blockade: effects of concurrent D2 blockade.
BACKGROUND
Prefrontal D1 systems have been implicated in the regulation of working memory and in the pathophysiology of schizophrenia. D1 hypofunction might contribute to reduced sensorimotor gating in schizophrenia patients since D1 activity in the medial prefrontal cortex (MPFC) regulates prepulse inhibition of startle (PPI) in animal models. We studied the neurochemical basis for the D1 regulation of PPI in rats.


METHODS
PPI to weak (1-5 dB over background) prepulses was measured after systemic or intra-MPFC administration of the D1 antagonist, SCH 23390, in rats pretreated systemically with the D2 antagonist, haloperidol (vehicle or 0.1 mg/kg).


RESULTS
After vehicle pretreatment, systemic and intra-MPFC SCH 23390 disrupted PPI produced by weak prepulses. This effect was not significantly opposed by pretreatment with haloperidol (0.1 mg/kg). In contrast, the PPI-disruptive effects of the DA agonist amphetamine were significantly opposed by this dose of haloperidol.


CONCLUSIONS
D1 blockade reduces PPI, but this effect does not appear to be mediated entirely via increased dopamine transmission at D2 receptors.
Swerdlow
Neal R
NR
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92037-0804, USA. nswerdlow@ucsd.edu
Shoemaker
Jody M
JM
Bongiovanni
Michele J
MJ
Neary
Alaina C
AC
Tochen
Laura S
LS
Saint Marie
Richard L
RL
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003864:Depression, Chemical; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D008297:Male; D017397:Prefrontal Cortex / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects*
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D000661:Amphetamine; D006220:Haloperidol