Dopaminergic and noradrenergic modulation of amphetamine-induced changes in auditory gating.
Dopaminergic and noradrenergic mediation of central sensory gating were assessed in Sprague-Dawley rats using a condition-test paradigm in which auditory evoked potentials were recorded. In this paradigm, unmedicated rats 'gate', i.e. suppress the response to the second of a pair of clicks delivered at a 0.5 s interval. Amphetamine-treated rats fail to gate; in this respect, they resemble schizophrenic humans. Previous studies had indicated noradrenergic involvement in the mediation of auditory gating in rats. In this study, we used selective antagonists to assess the contribution of alpha- and beta-adrenergic receptors, and dopamine D1- and D2-receptors, to amphetamine-induced alterations in gating. Both the alpha-antagonist, phentolamine, and the beta-antagonist, timolol, normalized gating by potentiating amphetamine-induced decreases in the amplitude of the test response. SCH 23390, a D1-receptor antagonist, also normalized gating, but by elevating the amphetamine-reduced amplitude of the conditioning response. Sulpiride did not significantly alter amphetamine-induced changes in gating. Thus, both noradrenergic alpha- and beta-receptors and dopamine D1-receptors appear to modulate gating. However, their dissimilar means of normalizing gating suggests that noradrenergic and dopaminergic drugs act via different mechanisms and possibly different neuroanatomical loci.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO.
K E
KE
Stevens
L L
LL
Fuller
G M
GM
Rose
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000661:Amphetamine; D004298:Dopamine; D009638:Norepinephrine