Locomotion and stereotypy induced by scopolamine: contributions of muscarinic receptors near the pedunculopontine tegmental nucleus.
In this study, we test whether blockade of muscarinic receptors near mesopontine cholinergic cell groups may contribute to locomotor activation induced by scopolamine. Unilateral or bilateral injections of scopolamine (10-150 micrograms) into the pedunculopontine tegmental nucleus (PPT) increased horizontal locomotion by 2-15 times in a dose-related way. Unilateral or bilateral injections of scopolamine into the PPT increased stereotypic behaviors (such as sniffing in one location or over large areas), self-biting and grooming. Carbachol (4 micrograms) injected into PPT reduced locomotion for 20 min, followed by 70 min of increased locomotion. When carbachol (4 micrograms) was injected into the PPT before scopolamine (3 mg/kg, i.p.), the activating effect of scopolamine was attenuated, but not when carbachol was injected after scopolamine. Therefore, carbachol appears to compete with scopolamine for muscarinic receptors near the PPT that mediate locomotor activating effects of systemic scopolamine. Haloperidol (0.1 mg/kg, i.p.) also attenuated the stereotypy and locomotion induced by scopolamine in the PPT. We hypothesize that scopolamine acts by blocking muscarinic receptors on mesopontine cholinergic neurons, thereby disinhibiting cholinergic neurons that can activate dopamine neurons.
Mathur
A
A
Department of Psychology, University of Toronto, Ont., Canada.
Shandarin
A
A
LaViolette
S R
SR
Parker
J
J
Yeomans
J S
JS
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D002217:Carbachol; D012601:Scopolamine; D006220:Haloperidol