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Reduced startle gating after D1 blockade: effects of concurrent D2 blockade
Neal R Swerdlow1, Jody M Shoemaker, Michele J Bongiovanni
1Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92037-0804, USA. nswerdlow@ucsd.edu
Pharmacology, Biochemistry, and Behavior
|September 29, 2005
Summary
Dopamine D1 receptor blockade impairs sensorimotor gating (prepulse inhibition) in rats, suggesting this pathway is crucial for normal gating function. This effect is not fully explained by changes in D2 receptor activity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Prefrontal D1 systems are vital for working memory and implicated in schizophrenia.
- D1 receptor hypofunction may underlie reduced sensorimotor gating in schizophrenia.
- Medial prefrontal cortex (MPFC) D1 activity regulates prepulse inhibition of startle (PPI) in animal models.
Purpose of the Study:
- To investigate the neurochemical basis of D1 receptor regulation of PPI.
- To determine if D1 blockade's effect on PPI is mediated by D2 receptors.
Main Methods:
- Administered D1 antagonist SCH 23390 systemically and intra-MPFC in rats.
- Pretreated rats with D2 antagonist haloperidol or vehicle.
- Measured PPI to weak prepulses.
Main Results:
- Systemic and intra-MPFC SCH 23390 disrupted PPI.
- Haloperidol pretreatment did not significantly oppose SCH 23390's PPI-disruptive effects.
- Haloperidol opposed the PPI-disruptive effects of amphetamine.
Conclusions:
- D1 receptor blockade reduces PPI in rats.
- The D1 receptor's role in PPI is not solely mediated by increased dopamine transmission at D2 receptors.