Alterations of striatal cholinergic receptors after lesioning of the substantia nigra.
Dopamine deficiency syndrome is known to cause cholinergic hyperactivity. Therefore, it was hypothesized that the said phenomenon may be due to enhanced cholinergic receptor functions. In the present study we examined the changes in striatal dopaminergic and cholinergic receptors in unilateral substantia nigra lesioned rats that showed vigorous ipsilateral rotation (total turns > 300) in response to apomorphine (1 mg kg(-1) ip). [3H] Spiperone ([3H]-SP) and [3H]-quinuclidinyl benzilate ([3H]-QNB) bindings were performed in the striata of the lesioned animals. There was no significant difference in the dissociation equilibrium constant values (Kd) between the lesioned and non-lesioned sides. However, a significant difference in the maximum receptor density (Bmax) of both [3H]-SP and [3H]-QNB bindings was observed between the lesioned and non-lesioned sides. The Bmax of [3H]-SP binding was significantly decreased on the lesioned side, whereas the Bmax of the [3H]-QNB binding was significantly increased. These results support the hypothesis that deficiencies of the dopaminergic system cause overactivity of the cholinergic system in the striatum.
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Y
Y
Sanvarinda
L
L
Phivthongngam
P
P
Govitrapong
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism; D004598:Electrosurgery; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013378:Substantia Nigra / Q000502:physiology* / Q000601:surgery
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D013134:Spiperone; D011813:Quinuclidinyl Benzilate; D001058:Apomorphine