Sensitivity to the dopaminergic regulation of prepulse inhibition in rats: Evidence for genetic, but not environmental determinants

Swerdlow, Neal R.; Platten, Amanda; Kim, Y.K; Gaudet, I; Shoemaker, Jody M.; Pitcher, Leia; Auerbach, Pamela P.

doi:10.1016/s0091-3057(01)00598-6

Cited by 62 publications

(64 citation statements)

References 31 publications

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“…We previously reported greater sensitivity of SD than LE rats to the PPI-disruptive effects of systemically administered DAergic agonists, including APO, d-amphetamine and quinpirole (Swerdlow et al, 2001b;2004a;2004b;2004c). These studies demonstrated the effects of dopamine agonists on PPI under conditions in which both prepulse and pulse were acoustic stimuli.…”

Section: Discussionmentioning

confidence: 97%

“…For example, Sprague Dawley rats from Harlan Laboratories (SD) are significantly more sensitive to the PPI-disruptive effects of dopamine (DA) agonists such as APO, compared to Long Evans rats from Harlan Laboratories (LE) (Swerdlow et al, 2001b;2004a;2004b;2004c). These differences have been shown to be innate (Swerdlow et al, 2004a;2004c) and neurochemically specific (Swerdlow et al, 2003;2004b), cannot be explained by differences in maternal behavior (Swerdlow et al, 2004a), and appear to be linked to inherited properties of DA-linked G-protein function .…”

Section: Introductionmentioning

confidence: 99%

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Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses

Weber

Swerdlow²

2008

Pharmacology Biochemistry and Behavior

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Prepulse inhibition of startle (PPI) is an operational measure of sensorimotor gating that is impaired in schizophrenia and is disrupted in rats by dopamine (DA) agonists like apomorphine (APO). Using acoustic prepulses and acoustic startle pulses, previous studies have demonstrated heritable strain differences between Sprague Dawley (SD) and Long Evans (LE) rats in the sensitivity to the PPIdisruptive effects of APO. As PPI deficits in schizophrenia are evident with both uni-and crossmodal stimuli, we tested whether strain differences in the gating-disruptive effects of APO occur with a cross-modal visual and acoustic stimulus combination. APO caused a dose-dependent disruption of both acoustic and visual PPI in SD rats. Compared to LE rats, SD rats were more sensitive to the PPI-disruptive effects of APO with both acoustic and visual PPI. These findings suggest that SD vs. LE strain differences in PPI APO sensitivity are mediated outside of the auditory system, within higher circuitry that regulates or processes multi-modal information. The present findings provide further validation for this heritable model of impaired sensorimotor gating in schizophrenia, which can be detected across multiple sensory modalities.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses

Weber

Swerdlow²

2008

Pharmacology Biochemistry and Behavior

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“…A careful assessment of the effects of dopaminergic drugs on human PPI reveals that the indirect DA agonist amphetamine reduced PPI only in specific subgroups of humans, distinguished by their smoking history (Kumari et al, 1998) or personality features . That different subsets of humans might be more or less sensitive to these PPI-disruptive effects is not surprising, given the ample preclinical evidence for infrahuman strain differences in sensitivity to the PPI-disruptive effects of DA agonists (Swerdlow et al, 2000b(Swerdlow et al, , 2001c. One report of reduced PPI in humans treated with the D2 blocker haloperidol (Abduljawad et al, 1998) is also at odds with the predominant effect of haloperidol on PPI in rats (Mansbach et al, 1988;Swerdlow et al, 1994;cf Swerdlow and Geyer, 1998;cf Geyer et al, 2001), although we have also occasionally observed PPI-reducing effects of this drug in rats, particularly juveniles (Martinez et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Amphetamine Effects on Prepulse Inhibition Across-Species: Replication and Parametric Extension

Swerdlow

Stephany

Wasserman

et al. 2002

Neuropsychopharmacol

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Despite the similarities of prepulse inhibition (PPI) of the startle reflex and its apparent neural regulation in rodents and humans, it has been difficult to demonstrate cross-species homology in the sensitivity of PPI to pharmacologic challenges. PPI is disrupted in rats by the indirect dopamine (DA) agonist amphetamine, and while studies in humans have suggested similar effects of amphetamine, these effects have been limited to populations characterized by smoking status and specific personality features. In the context of a study assessing the time course of several DA agonist effects on physiological variables, we failed to detect PPI-disruptive effects of amphetamine in a small group of normal males. The present study was designed to reexamine this issue, using a larger sample and a paradigm that should be more sensitive for detecting drug effects. PPI in rats was shown to be disrupted by the highest dose of amphetamine (3.0 mg/kg) at relatively longer prepulse intervals (430 ms). In humans, between-subject comparisons of placebo (n ¼ 15) vs 20 mg amphetamine (n ¼ 15) failed to detect significant PPI-disruptive effects of amphetamine, but significant PPI-disruptive effects at short (10-20 ms) prepulse intervals were detected using within-subject analyses of postdrug PPI levels relative to each subject's baseline PPI. Post hoc comparisons failed to detect greater sensitivity to amphetamine among subjects characterized by different personality and physiological traits. Bioactivity of amphetamine was verified by autonomic and subjective changes. These results provide modest support for crossspecies homology in the PPI-disruptive effects of amphetamine, but suggest that these effects in humans at the present dose are subtle and may be best detected using within-subject designs and specific stimulus characteristics.

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“…Although abundant literature exists describing the dopamine mechanisms regulating PPI in rats, there are relatively few reports describing comparable studies across different strains of mice. It has been well established in rats that D2-like agonists such as quinpirole, 7-OH-DPAT, and quinelorane reliably disrupt PPI in outbred rats (Peng et al, 1990;Caine et al, 1995;Varty and Higgins, 1998;Swerdlow et al, 2000Swerdlow et al, , 2001b, whereas effects of the D1-like agonists SKF38393 and SKF82958 were more variable and strainspecific (Peng et al, 1990;Wan et al, 1996;Swerdlow et al, 2000Swerdlow et al, , 2001b. However, in inbred C57BL6/J and 129S6/SvEv mice, the D2-like agonist quinpirole did not decrease PPI over a wide dose range (Ralph-Williams et al, 2003), whereas D1-like agonists such as SKF82958, SKF81297, and dihydrexidine robustly decreased PPI in those strains and in a hybrid F2 line of closely related strains (Holmes et al, 2001;Ralph-Williams et al, 2003).…”

mentioning

confidence: 99%

Dopamine D1 and D2 Agonist Effects on Prepulse Inhibition and Locomotion: Comparison of Sprague-Dawley Rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J Mice

Ralph

Caine

2004

J Pharmacol Exp Ther

120

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D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and the D1-like agonist R-6-Br-APB [R(ϩ)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/ kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in SpragueDawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(Ϫ)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-(1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans.Prepulse inhibition (PPI) of the acoustic startle response is a cross-species phenomenon in which the startle response is reduced when the startling stimulus is preceded by a lowintensity prepulse (Graham, 1975;Hoffman and Ison, 1980). Although abundant literature exists describing the dopamine mechanisms regulating PPI in rats, there are relatively few reports describing comparable studies across different strains of mice. It has been well established in rats that D2-like agonists such as quinpirole, 7-OH-DPAT, and quinelorane reliably disrupt PPI in outbred rats (Peng et al., 1990;Caine et al., 1995;Varty and Higgins, 1998;Swerdlow et al., 2000Swerdlow et al., , 2001b, whereas effects of the D1-like agonists SKF38393 and SKF82958 were more variable and strainspecific (Peng et al., 1990;Wan et al., 1996;Swerdlow et al., 2000Swerdlow et al., , 2001b. However, in inbred C57BL6/J and 129S6/SvEv mice, the D2-like agonist quinpirole did not decrease PPI over a wide dose range (Ralph-Williams et al., 2003), whereas D1-like agonists such as SKF82958, SKF81297, and dihydrexidine robustly decreased PPI in those strains and in a hybrid F2 line of closely related strains (Holmes et al., 2001;Ralph-Williams et al., 2003). Furthermore, the mixed D1/D2 receptor agonis...

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Sensitivity to the dopaminergic regulation of prepulse inhibition in rats: Evidence for genetic, but not environmental determinants

Cited by 62 publications

References 31 publications

Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses

Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses

Amphetamine Effects on Prepulse Inhibition Across-Species: Replication and Parametric Extension

Dopamine D1 and D2 Agonist Effects on Prepulse Inhibition and Locomotion: Comparison of Sprague-Dawley Rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J Mice

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