Comparison of behavioral and central BDZ binding profile in three rat lines.
The performance of three widely used rat lines (Sprague-Dawley, Wistar, and Long Evans hooded) were evaluated in behavioral test systems that are sensitive to benzodiazepines. The in vivo effects of flunitrazepam and the brain [3H]Ro 15-1788 binding were determined and compared in these rat lines. The behavioral end points evaluated in this study were anxiolysis, measured using the automated elevated plus-maze; sedation by modification of locomotor activity; hyperphagia following food deprivation; protection for pentylenetetrazol-induced convulsions; and hypothermia. There were comparable results in the hypnotic, hypothermic, anticonvulsant, and feeding tests in these lines following flunitrazepam administration. However, the behavior of the Long Evans hooded rat was most amenable to the detection of drug-induced changes in the anxiety test. There was no difference in the maximum number of binding sites (Bmax) or the affinity (Ki) of the Ro 15-1788 or flunitrazepam binding in either the cerebellum or whole brain (minus cerebellum) in the three rat lines as determined by the competitive binding against [3H]Ro 15-1788. Thus, while these rat lines exhibited similar behavioral profiles in most tests the modest differences in the baseline responses and the ability to detect anxiolysis at lower doses of flunitrazepam observed with Long Evans hooded rats makes them particularly suited for these types of studies.
Molecular Research Institute, Palo Alto, CA 94304.
E S
ES
Onaivi
P A
PA
Maguire
N F
NF
Tsai
M F
MF
Davies
G H
GH
Loew
D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005442:Flumazenil / Q000493:pharmacokinetics / Q000494:pharmacology; D005445:Flunitrazepam / Q000493:pharmacokinetics / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013045:Species Specificity
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; D010433:Pentylenetetrazole