Ontogeny of muscarinic cholinergic supersensitivity in the Flinders Sensitive Line rat.
The present study examined the ontogeny of muscarinic sensitivity in the Flinders Sensitive Line (FSL) rat, a model for human depression that was selectively bred for increased cholinergic function. In most cases, the FSL rats were more sensitive to the muscarinic agonists, oxotremorine and oxotremorine-M. early postnatally [13 days postpartum (P13)], suggesting that muscarinic supersensitivity is an inherent characteristic of FSL rats. The emergence of increased sensitivity to muscarinic agonists in FSL rats did not correlate with either the emergence of subsensitivity to the muscarinic antagonist, scopolamine, at P60 or with increased muscarinic (M1 or M2) receptor density. Relative to FRL rats, FSL rats did not exhibit increases in muscarinic receptor binding until P32 in the striatum and hippocampus and P120 in the hypothalamus. These results are consistent with the suggestions that (a) muscarinic supersensitivity, which appears early in development, may be associated with depressive disorders, and (b) the differences in muscarinic sensitivity early postnatally cannot be accounted for by an increase in the number of muscarinic receptors, per se.
Daws
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LC
The Flinders University of South Australia, Department of Science and Engineering, School of Biological Sciences, Adelaide, Australia.
Overstreet
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DH
D000818:Animals; D001665:Binding Sites; D001831:Body Temperature / Q000187:drug effects; D003863:Depression / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism