Quinelorane, a dopamine D3/D2 receptor agonist, reduces prepulse inhibition of startle and ventral pallidal GABA efflux: time course studies.
Startle is inhibited when the startling stimulus is preceded 30-300 ms by a weak prepulse. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is deficient in schizophrenia patients, and reduced in rats and humans by dopamine agonists. The neural basis for the PPI-disruptive effects of dopamine agonists in rats is studied to understand neural circuitry regulating PPI and its deficits in schizophrenia. Existing data suggest that ventral pallidal (VP) GABAergic transmission regulates PPI and its disruption by dopamine agonists. We measured changes in VP GABA efflux and PPI in rats in response to the D2/D3 agonist, quinelorane. Wistar rats were administered quinelorane (vehicle, 0.003 or 0.01 mg/kg). In some rats, VP dialysate was analyzed for GABA content. In others, PPI was assessed using 120 dB(A) startle pulses and prepulses 10 dB over a 70 dB(A) background. Quinelorane reduced GABA efflux, with significant effects for 0.01 but not 0.003 mg/kg, persisting for at least 100 min. Quinelorane reduced PPI for 50 min, an effect significant for both the 0.003 (p < 0.05) and 0.01 mg/kg doses (p < 0.015). Differences in time course and dose sensitivity of quinelorane effects on VP GABA efflux and PPI are discussed.
Qu
Ying
Y
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA.
Swerdlow
Neal R
NR
Weber
Martin
M
Stouffer
David
D
Parsons
Loren H
LH
D000818:Animals; D003627:Data Interpretation, Statistical; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018491:Dopamine Agonists; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D005680:gamma-Aminobutyric Acid; C047726:quinelorane