Alterations in cortical muscarinic receptors following cholinotoxin (AF64A) lesion of the rat nucleus basalis magnocellularis.
Cortical choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), muscarinic receptors and sodium-dependent, high-affinity, choline uptake (SDHACU) sites were examined in the rat brain following unilateral stereotaxic injection of the cholinotoxin, AF64A, into the nucleus basalis magnocellularis (NBM). Injection of AF64A resulted in a significant loss of presynaptic cholinergic markers in the cortex without alteration in TH and TPH activity. The binding to SDHACU sites was reduced to background values in the NBM and increased in the central amygdala (Ce) and cortex. The increase in cortical [3H]QNB binding was the result of a change in muscarinic receptor number (BMAX) and not a change in receptor affinity (KD). Examination of muscarinic receptor subtypes demonstrated a reduction of M1 receptor binding in the cortex and NBM without any alteration in the Ce. Non-M1 binding was significantly increased in all the laminae of the cortex and in the Ce, but decreased in the NBM. These data suggest that there exists a population of M1 receptors on NBM projections to the cortex and that NBM projections influence a population of postsynaptic receptors in the cortex and Ce which are not of the M1 subtype.
Department of Psychiatry, University of Utah, Salt Lake City 84132.
V L
VL
Dawson
M E
ME
Hunt
J K
JK
Wamsley
D000679:Amygdala / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001388:Aziridines / Q000633:toxicity*; D001479:Basal Ganglia / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000633:toxicity*; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014793:Visual Cortex / Q000201:enzymology / Q000378:metabolism
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; C044894:ethylcholine aziridinium; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D002794:Choline