Neural basis for a heritable phenotype: differences in the effects of apomorphine on startle gating and ventral pallidal GABA efflux in male Sprague-Dawley and Long-Evans rats.
BACKGROUND
Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is heritable and deficient in certain psychiatric disorders, including schizophrenia. Sprague-Dawley (SD) rats are more sensitive to PPI disruptive effects of dopamine (DA) agonists at long interstimulus intervals (60-120 ms) and less sensitive to their PPI-enhancing effects at short (10-30 ms), compared with Long-Evans (LE) rats. These heritable strain differences in sensitivity to the PPI disruptive effects of DA agonists must ultimately reflect neural changes "downstream" from forebrain DA receptors.


OBJECTIVE
The current study evaluated the effects of the DA agonist, apomorphine (APO), on ventral pallidal (VP) gamma-aminobutyric acid (GABA) and glutamate efflux and PPI in SD and LE rats.


METHODS
PPI was tested in SD and LE rats after vehicle or APO (0.5 mg/kg, subcutaneously (s.c.)) in a within-subject design. In different SD and LE rats, VP dialysate was collected every 10 min for 120 min after vehicle or APO (0.5 mg/kg, s.c.) and analyzed for GABA and glutamate content by capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF).


RESULTS
As predicted, SD rats exhibited greater APO-induced PPI deficits at long intervals and less APO-induced PPI enhancement at short intervals compared to LE rats. APO significantly reduced VP GABA efflux in SD but not in LE rats; glutamate efflux was unaffected in both strains.


CONCLUSIONS
Heritable strain differences in PPI APO sensitivity in SD vs LE rats parallel, and may be mediated by, strain differences in the VP GABA efflux.
Qu
Ying
Y
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA.
Saint Marie
Richard L
RL
Breier
Michelle R
MR
Ko
David
D
Stouffer
David
D
Parsons
Loren H
LH
Swerdlow
Neal R
NR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D019075:Electrophoresis, Capillary; D005453:Fluorescence; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D010641:Phenotype; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D055139:Sensory Gating / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D018491:Dopamine Agonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001058:Apomorphine