Amygdaloid N-methyl-D-aspartate and gamma-aminobutyric acid(A) receptors regulate sensorimotor gating in a dopamine-dependent way in rats.
Sensorimotor gating can be measured as prepulse inhibition of the startle response in humans and rats. Since prepulse inhibition is impaired in schizophrenics there is considerable interest in understanding the neuronal basis of prepulse inhibition. Neuropathological findings indicate a dysfunction of the glutamatergic and GABAergic system in cortico-limbic areas in schizophrenics. We tested whether blockade of N-methyl-D-aspartate or GABA(A) receptors in the basolateral amygdala affects prepulse inhibition in rats. Local infusion of the N-methyl-D-aspartate receptor antagonist dizocilpine (0, 6.25 microg/0.5 microl), or of the GABA(A) receptor antagonist picrotoxin (0, 5.0, 10.0 ng/0.5 microl) reduced prepulse inhibition. The prepulse inhibition-disrupting effect of 6.25 microg dizocilpine or 10.0 ng picrotoxin was reversed by systemic co-administration of the dopamine antagonist haloperidol (0.1mg/kg i.p.). These data indicate that sensorimotor gating is regulated in a dopamine-dependent way by N-methyl-D-aspartate and GABA(A) receptors in the basolateral amygdala. Our findings are discussed with respect to neuropathological findings in schizophrenics.
Fendt
M
M
Tierphysiologie, Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
Schwienbacher
I
I
Koch
M
M
D000679:Amygdala / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology
D016291:Dizocilpine Maleate; D004298:Dopamine; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D006220:Haloperidol; D010852:Picrotoxin; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate