![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
VP Bakshi, NR Swerdlow and MA Geyer
Department of Psychiatry, University of California at San Diego School of Medicine.
Intense auditory stimuli elicit an involuntary startle response that is attenuated when the startling stimulus (the pulse) is preceded immediately by a low intensity stimulus (the prepulse). This phenomenon of prepulse inhibition (PPI) is utilized as a measure of sensorimotor gating and is significantly reduced in schizophrenic patients. Noncompetitive N-methyl-D-aspartate antagonists such as phencyclidine (PCP) and ((+)-D-aspartate 5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine) (dizocilpine, or MK-801) have been found previously to disrupt PPI in animals. The present investigation assessed the ability of several antipsychotic drugs to reverse PCP- induced deficits in PPI in rats. Animals were pretreated with either the atypical antipsychotic clozapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg), the D2 dopamine antagonist raclopride (0, 0.1 or 0.5 mg/kg), the D1 dopamine antagonist SCH23390 (0, 0.01 or 0.05 mg/kg) or the 5- hydroxytryptamine2 antagonists ritanserin (0 or 2.0 mg/kg) or ketanserin (0 or 1.0 mg/kg) and then were given PCP (1.0 mg/kg). After drug administration, animals were tested in startle chambers. PCP repeatedly and robustly decreased PPI without affecting base-line startle reactivity. Clozapine (5.0 mg/kg) antagonized this effect of PCP without altering PPI by itself. Raclopride, SCH23390, ritanserin and ketanserin were ineffective at reversing the PCP-induced deficit in PPI. As with PCP, 0.1 mg/kg of MK-801 disrupted PPI; this disruption also was antagonized by 5.0 mg/kg of clozapine. Thus, it appears that the ability of clozapine to reverse deficits in PPI produced by noncompetitive N-methyl-D-aspartate antagonists cannot be attributed to a sole antagonism of either D1 dopamine, D2 dopamine or 5- hydroxytryptamine2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  S. J. Graham, J. C. Scaife, A. M. B. Verduzco, R. W. Langley, C. M. Bradshaw, and E. Szabadi Effects of Quetiapine and Haloperidol on Prepulse Inhibition of the Acoustic Startle (Eyeblink) Response and the N1/P2 Auditory Evoked Response in Man J Psychopharmacol, June 1, 2004; 18(2): 173 - 180. [Abstract] [PDF]
|
|
|
|
 |
|
 G. E. Duncan, S. Miyamoto, and J. A. Lieberman Chronic Administration of Haloperidol and Olanzapine Attenuates Ketamine-Induced Brain Metabolic Activation J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 999 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, J. McInnis, J. B. West, J. Bao, N. Anastasio, J. A. Guidry, Y. Ye, D. Salvemini, and K. M. Johnson Blockade of Phencyclidine-Induced Cortical Apoptosis and Deficits in Prepulse Inhibition by M40403, a Superoxide Dismutase Mimetic J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 266 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Ralph-Williams, V. Lehmann-Masten, V. Otero-Corchon, M. J. Low, and M. A. Geyer Differential Effects of Direct and Indirect Dopamine Agonists on Prepulse Inhibition: A Study in D1 and D2 Receptor Knock-Out Mice J. Neurosci., November 1, 2002; 22(21): 9604 - 9611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Weiner, E. S. Burstein, N. Nash, G. E. Croston, E. A. Currier, K. E. Vanover, S. C. Harvey, E. Donohue, H. C. Hansen, C. M. Andersson, et al. 5-Hydroxytryptamine2A Receptor Inverse Agonists as Antipsychotics J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 268 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Goff and J. T. Coyle The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia Am J Psychiatry, September 1, 2001; 158(9): 1367 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Umbricht, L. Schmid, R. Koller, F. X. Vollenweider, D. Hell, and D. C. Javitt Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers: Implications for Models of Cognitive Deficits in Schizophrenia Arch Gen Psychiatry, December 1, 2000; 57(12): 1139 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Duncan, S. Miyamoto, J. N. Leipzig, and J. A. Lieberman Comparison of the Effects of Clozapine, Risperidone, and Olanzapine on Ketamine-Induced Alterations in Regional Brain Metabolism J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 8 - 14. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Geyer, N. R. Swerdlow, V. Lehmann-Masten, H.-J. Teschendorf, M. Traut, and G. Gross Effects of LU-111995 in Three Models of Disrupted Prepulse Inhibition in Rats J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 716 - 724. [Abstract] [Full Text]
|
|
|
|
|
|
D. L. Braff, N. R. Swerdlow, and M. A. Geyer Symptom Correlates of Prepulse Inhibition Deficits in Male Schizophrenic Patients Am J Psychiatry, April 1, 1999; 156(4): 596 - 602. [Abstract] [Full Text]
|
|
|
|
|
|
V. P. Bakshi, M. Tricklebank, H. C. Neijt, V. Lehmann-Masten, and M. A. Geyer Disruption of Prepulse Inhibition and Increases in Locomotor Activity by Competitive N-Methyl-D-aspartate Receptor Antagonists in Rats J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 643 - 652. [Abstract] [Full Text]
|
|
|
|
|
|
D. Feifel, T. L. Reza, D. J. Wustrow, and M. D. Davis Novel Antipsychotic-Like Effects on Prepulse Inhibition of Startle Produced by a Neurotensin Agonist J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 710 - 713. [Abstract] [Full Text]
|
|
|
|
|
|
V. P. Bakshi and M. A. Geyer Multiple Limbic Regions Mediate the Disruption of Prepulse Inhibition Produced in Rats by the Noncompetitive NMDA Antagonist Dizocilpine J. Neurosci., October 15, 1998; 18(20): 8394 - 8401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Adams and B. Moghaddam Corticolimbic Dopamine Neurotransmission Is Temporally Dissociated from the Cognitive and Locomotor Effects of Phencyclidine J. Neurosci., July 15, 1998; 18(14): 5545 - 5554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sallinen, A. Haapalinna, T. Viitamaa, B. K. Kobilka, and M. Scheinin Adrenergic alpha 2C-Receptors Modulate the Acoustic Startle Reflex, Prepulse Inhibition, and Aggression in Mice J. Neurosci., April 15, 1998; 18(8): 3035 - 3042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Bakshi and M. A. Geyer Phencyclidine-Induced Deficits in Prepulse Inhibition of Startle are Blocked by Prazosin, an Alpha-1 Noradrenergic Antagonist J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 666 - 674. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
