TY - JOUR
T1 - Cholinergic/serotonergic interactions in hypothermia
T2 - Implications for rat models of depression
AU - Overstreet, David H.
AU - Daws, Lynette C.
AU - Schiller, Grant D.
AU - Orbach, Joe
AU - Janowsky, David S.
N1 - Funding Information:
This work was supported in part by an NH & MRC Biomedical Postgraduate Scholarship (Grant 927435) awarded to L. C. Daws, and by the Flinders University Research Budget. The authors would like to thank Cheryl Greaves and Leah Nesbitt for excellent care and maintenance of the animals and to Mr. George Daws for assistance.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/4
Y1 - 1998/4
N2 - This article reviews published reports and presents new evidence that support a number of commonalties between lines of rats selectively bred for differences in cholinergic (muscarinic) and serotonergic (5-HT(1A) sensitivity. The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression derived for cholinergic supersensitivity is more sensitive to both cholinergic and serotonergic agonists, and exhibits exaggerated immobility in the forced swim lest relative to the control. Flinders Resistant Line (FRL), rat. Similar exaggerated responses are seen in a line of rats recently selected fur increased sensitivity to the 5-HT(1A) agonist, 8-OH-DPAT (High DPAT Sensitive - HDS), relative to lines selectively bred for either low (Low DPAT Sensitive - LDS) or random (Random DPAT Sensitive RDS) sensitivity to 8- OH-DPAT. For both the FSL and HDS rats, their exaggerated immobility in the forced swim test is reduced following chronic treatment with anti- depressants. The present studies examined further the interaction between cholinergic and serotonergic systems in the above lines. Supersensitive hypothermic responses to 8-OH-DPAT were observed very early (postnatal day 18) in FSL rats, suggesting that both muscarinic and serotonergic supersensitivity are inherent characteristics of these rats. Scopolamine, a muscarinic antagonist, completely blocked the hypothermic effects of the muscarinic agonist oxotremorine in FSL and FRL rats, but had no effect on the hypothermic responses to 8-OH-DPAT, suggesting an independence of muscarinic and 5-HT(1A) systems. On the other hand, genetic selection of genetically heterogeneous rats for differential hypothermic responses to the muscarinic agonist oxotremorine were accompanied by differential hypothermic responses to 8-OH-DPAT, suggesting an interaction between muscarinic and 5-HT(1A) systems. Overall, these studies argue for an inherent interaction between muscarinic and 5-HT(1A) systems, which probably occurs beyond the postsynaptic receptors, possibly at the level of G proteins.
AB - This article reviews published reports and presents new evidence that support a number of commonalties between lines of rats selectively bred for differences in cholinergic (muscarinic) and serotonergic (5-HT(1A) sensitivity. The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression derived for cholinergic supersensitivity is more sensitive to both cholinergic and serotonergic agonists, and exhibits exaggerated immobility in the forced swim lest relative to the control. Flinders Resistant Line (FRL), rat. Similar exaggerated responses are seen in a line of rats recently selected fur increased sensitivity to the 5-HT(1A) agonist, 8-OH-DPAT (High DPAT Sensitive - HDS), relative to lines selectively bred for either low (Low DPAT Sensitive - LDS) or random (Random DPAT Sensitive RDS) sensitivity to 8- OH-DPAT. For both the FSL and HDS rats, their exaggerated immobility in the forced swim test is reduced following chronic treatment with anti- depressants. The present studies examined further the interaction between cholinergic and serotonergic systems in the above lines. Supersensitive hypothermic responses to 8-OH-DPAT were observed very early (postnatal day 18) in FSL rats, suggesting that both muscarinic and serotonergic supersensitivity are inherent characteristics of these rats. Scopolamine, a muscarinic antagonist, completely blocked the hypothermic effects of the muscarinic agonist oxotremorine in FSL and FRL rats, but had no effect on the hypothermic responses to 8-OH-DPAT, suggesting an independence of muscarinic and 5-HT(1A) systems. On the other hand, genetic selection of genetically heterogeneous rats for differential hypothermic responses to the muscarinic agonist oxotremorine were accompanied by differential hypothermic responses to 8-OH-DPAT, suggesting an interaction between muscarinic and 5-HT(1A) systems. Overall, these studies argue for an inherent interaction between muscarinic and 5-HT(1A) systems, which probably occurs beyond the postsynaptic receptors, possibly at the level of G proteins.
KW - 8-OH-DPAT
KW - Core body temperature
KW - Depression
KW - FSL rat
KW - Muscarinic
KW - Ontogeny
KW - Oxotremorine
KW - Serotonin
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UR - http://www.scopus.com/inward/citedby.url?scp=0032052196&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(97)00514-5
DO - 10.1016/S0091-3057(97)00514-5
M3 - Article
C2 - 9586831
AN - SCOPUS:0032052196
VL - 59
SP - 777
EP - 785
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 4
ER -