TY - JOUR
T1 - Ontogeny of muscarinic cholinergic supersensitivity in the flinders sensitive line rat
AU - Daws, Lynette C.
AU - Overstreet, David H.
N1 - Funding Information:
This work was supported by a Dora Lush National Health and Medical Research Council Biomedical Postgraduate Scholarship (927435) to L.C.D. and funds provided by the Flinders University Research Budget. The authors would like to greatfully acknowledge Cheryl Greaves and Leah Nesbitt for their excellent care and maintenance of the animals and George Daws for research assistance. Our thanks to Drs Grant Schiller and Joe Orbach for valuable discussions and their assistance with this study.
PY - 1999/2
Y1 - 1999/2
N2 - 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. Copyright (C) 1999 Elsevier Science Inc.
AB - 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. Copyright (C) 1999 Elsevier Science Inc.
KW - Core body temperature
KW - Depression
KW - FSL rats
KW - Locomotor activity
KW - Muscarinic receptors
KW - Oxotremorine
KW - Scopolamine
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U2 - 10.1016/S0091-3057(98)00174-9
DO - 10.1016/S0091-3057(98)00174-9
M3 - Article
C2 - 9972706
AN - SCOPUS:0032910699
SN - 0091-3057
VL - 62
SP - 367
EP - 380
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -