Ontogeny of muscarinic cholinergic supersensitivity in the Flinders Sensitive Line rat

The present study examined the ontogeny of muscarinic sensitivity in the Fl inders Sensitive Line (FSL) rat, a model for human depression that was sele ctively bred for increased cholinergic function. In most cases, the FSL rat s were more sensitive to the muscarinic agonists, oxotremorine and oxotremo rine-M, early postnatally [13 days postpartum (P13)], suggesting that musca rinic supersensitivity is an inherent characteristic of FSL rats. The emerg ence of increased sensitivity to muscarinic agonists in FSL rats did not co rrelate with either the emergence of subsensitivity to the muscarinic antag onist, scopolamine, at P60 or with increased muscarinic (M1 or M2) receptor density. Relative to FRL rats, FSL rats did not exhibit increases in musca rinic receptor binding until P32 in the striatum and hippocampus and P120 i n 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 muscarini c sensitivity early postnatally cannot be accounted for by an increase in t he number of muscarinic receptors, per se. (C) 1999 Elsevier Science Inc.