Heritable differences in the dopaminergic regulation of sensorimotor gating - II. Temporal, pharmacologic and generational analyses of apomorphine effects on prepulse inhibition

被引：44

作者：

Swerdlow, NR ^{[1
]}

Shoemaker, JM ^{[1
]}

Auerbach, PP ^{[1
]}

Pitcher, L ^{[1
]}

Goins, J ^{[1
]}

Platten, A ^{[1
]}

机构：

[1] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA

来源：

PSYCHOPHARMACOLOGY | 2004年 / 174卷 / 04期

关键词：

apomorphine; dopamine; genetics; prepulse inhibition; schizophrenia; startle;

D O I：

10.1007/s00213-003-1480-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Rationale and objectives: The disruption of prepulse inhibition (PPI) of startle in rats by dopamine agonists has been used in a predictive model for antipsychotics, and more recently, to study the neural basis of strain differences in dopaminergic function. We have previously reported that Sprague-Dawley (SDH) and Long Evans (LEH) rats differed in their sensitivity to the PPI-disruptive effects of the D-1/D-2 agonist apomorphine (APO) in two distinct ways: 1) compared to LEH rats, SDH rats were more sensitive to the ability of APO to disrupt PPI with relatively long prepulse intervals (60-120 ms), and 2) APO enhanced PPI in LEH rats with 10-30 ms prepulse intervals, but this effect was limited to 10 ms prepulse intervals in SDH rats. Methods: In the present study, we replicated this temporal profile in SDH versus LEH rats, assessed the role of D-1 versus D-2 substrates in the two components of this strain difference, and assessed the heritability of these temporally distinct processes. Results: Pharmacologic studies revealed that: 1) D-2 blockade prevented the long interval PPI-disruptive effects of APO in both strains, and extended the temporal range of the PPI-enhancing effects of APO from 10 to 30 ms in SDH rats, and 2) D-1 blockade increased PPI and blocked the PPI-enhancing effects of APO at short intervals in both strains. Generational studies in adult F0 (SDH and LEH), F1 (SDHxLEH) and N2 (SDHxF1) rats demonstrated that sensitivity to APO of both short and long interval PPI were inherited in a manner suggestive of relatively simple additive effects of multiple genes. Conclusions: The present findings demonstrate that inherited differences in the dopaminergic regulation of sensorimotor gating are manifested not only in quantitative shifts (more versus less), but also in qualitative shifts in the temporal properties of sensorimotor gating that appear to be under separate control of D-1 and D-2 substrates.

引用

页码：452 / 462

页数：11

共 36 条

[1]

ABDULJAWAD KAJ, 1997, J PSYCHOPHARMACOL, V11, P69

[2]

Amicarelli F, 1999, CELL MOL BIOL, V45, P1093

[3]

[Anonymous], [No title captured]

[4] PRE-STIMULUS EFFECTS ON HUMAN STARTLE REFLEX IN NORMALS AND SCHIZOPHRENICS [J].

BRAFF, D ;

STONE, C ;

CALLAWAY, E ;

GEYER, M ;

GLICK, I ;

BALI, L .

PSYCHOPHYSIOLOGY, 1978, 15 (04) :339-343

[5] Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies [J].

Braff, DL ;

Geyer, MA ;

Swerdlow, NR .

PSYCHOPHARMACOLOGY, 2001, 156 (2-3) :234-258

[6] PETIT-MAL EPILEPSY AND PARKINSONIAN TREMOR - HYPOTHESIS OF A COMMON PACEMAKER [J].

BUZSAKI, G ;

SMITH, A ;

BERGER, S ;

FISHER, LJ ;

GAGE, FH .

NEUROSCIENCE, 1990, 36 (01) :1-14

[7]

Carter RJ, 1999, J NEUROSCI, V19, P3248

[8] Auditory information processing in rat genotypes with different dopaminergic properties [J].

de Bruin, NMWJ ;

van Luijtelaar, ELJM ;

Cools, AR ;

Ellenbroek, BA .

PSYCHOPHARMACOLOGY, 2001, 156 (2-3) :352-359

[9] Dopamine characteristics in different rat genotypes: the relation to absence epilepsy [J].

de Bruin, NMWJ ;

van Luijtelaar, ELJM ;

Jansen, SJ ;

Cools, AR ;

Ellenbroek, BA .

NEUROSCIENCE RESEARCH, 2000, 38 (02) :165-173

[10] Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review [J].

Geyer, MA ;

Krebs-Thomson, K ;

Braff, DL ;

Swerdlow, NR .

PSYCHOPHARMACOLOGY, 2001, 156 (2-3) :117-154

← 1 2 3 4 →