Forebrain D1 function and sensorimotor gating in rats: effects of D1 blockade, frontal lesions and dopamine denervation

Neuroscience Letters
N R SwerdlowRichard L Saint Marie

Abstract

Prefrontal D1 hypoactivity is implicated in the pathophysiology of schizophrenia, and might contribute to sensorimotor gating deficits in schizophrenia patients, based on evidence that D1 blockade in the medial prefrontal cortex (MPFC) reduces prepulse inhibition of startle (PPI) in animal models. PPI is disrupted by systemic and intra-MPFC infusion of the D1 antagonist, SCH23390. We investigated the role of the MPFC in the PPI-disruptive effects of systemic SCH23390 administration, and more generally, in the dopaminergic regulation of PPI. PPI was measured in rats after forebrain manipulations, including systemic administration of SCH23390, ibotenic acid lesions of the MPFC, and 6OHDA-induced dopamine (DA) depletion from MPFC or nucleus accumbens. Systemic SCH23390 disrupted PPI; these effects were not opposed by ibotenic acid lesions of the MPFC. PPI remained intact after MPFC DA depletion, but--as predicted by Bubser and Koch [M. Bubser, M. Koch, Prepulse inhibition of the acoustic startle response of rats is reduced by 6 hydroxydopamine lesions of the medial prefrontal cortex, Psychopharmacology 113 (1994) 487-492]--a reduction in PPI from pre- to post-surgery correlated significantly with MPFC DA loss. The effects of syste...Continue Reading

References

Feb 20, 2004·The International Journal of Neuropsychopharmacology·Anissa Abi-Dargham
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Sep 24, 2004·Progress in Neurobiology·Jeremy K Seamans, Charles R Yang
Sep 29, 2005·Pharmacology, Biochemistry, and Behavior·Neal R SwerdlowRichard L Saint Marie

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Citations

Jul 2, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David KapfhamerUlrike Heberlein
Sep 11, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jonathan P FadokRichard D Palmiter
Sep 14, 2011·Journal of Visualized Experiments : JoVE·Bridget Valsamis, Susanne Schmid
Dec 8, 2009·Behavioural Brain Research·Osamu NakagawasaiTakeshi Tadano
Sep 22, 2007·Progress in Neuro-psychopharmacology & Biological Psychiatry·R E FeatherstoneP J Fletcher
Dec 16, 2006·Physiology & Behavior·Jack C TurvinMary F Kritzer
Apr 10, 2013·Pharmacology, Biochemistry, and Behavior·Neal R SwerdlowMichelle R Breier
Nov 21, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Neal R SwerdlowGregory A Light
May 28, 2017·Journal of Alzheimer's Disease : JAD·Alexandre V IvachtchenkoAndrey Ivashchenko
Feb 26, 2021·Developmental Psychobiology·Carly M DrzewieckiJanice M Juraska

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