ARE WISTAR-KYOTO RATS A GENETIC ANIMAL-MODEL OF DEPRESSION RESISTANT TO ANTIDEPRESSANTS

Citation
A. Lahmame et al., ARE WISTAR-KYOTO RATS A GENETIC ANIMAL-MODEL OF DEPRESSION RESISTANT TO ANTIDEPRESSANTS, European journal of pharmacology, 337(2-3), 1997, pp. 115-123
Citations number
55
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
337
Issue
2-3
Year of publication
1997
Pages
115 - 123
Database
ISI
SICI code
0014-2999(1997)337:2-3<115:AWRAGA>2.0.ZU;2-6
Abstract
Wistar-Kyoto rats are reported to be very passive in the forced swimmi ng test. In addition, they did not respond to acute administration of either desipramine or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPA T). In the present experiment, it was studied whether or not they resp ond to acute and chronic administration of imipramine and the possible relationship to down-regulation of beta-adrenoceptors and 5-HT1 and 5 -HT2 receptors. Sprague-Dawley and Brown-Norway rats were included in the study as it has been previously demonstrated that the two strains respond to acute desipramine and 8-OH-DPAT administration. Whereas acu te administration of imipramine (15 mg/kg, three times in a 21 h perio d) significantly increased struggling and reduced immobility in Spragu e-Dawley and Brown Norway rats, Wistar-Kyoto rats failed to respond to the drug. After chronic treatment with imipramine (13 days plus the a cute imipramine treatment at the end of the treatment period), the thr ee strains showed a positive response that was always significantly gr eater than the response to acute administration, but which was much lo wer in Wistar-Kyoto than in the other two strains. Down-regulation of both beta-adrenoceptors and 5-HT2 receptors was observed 24 h after th e forced swimming test in acutely and chronically imipramine-treated r ats of the three strains, except that in Sprague-Dawley rats beta-adre noceptors did not change after acute imipramine. No significant decrea se in 5-HT1 binding sites was observed in any strain. Acute imipramine administration caused a similar anorexia in Wistar-Kyoto as in the ot her strains and at least the same level of down-regulation of beta-adr enoceptors and 5-HT2 receptor. Tn addition, serum imipramine levels on the day after the last drug administration were higher in Wistar-Kyot o than in the other two strains. All these data suggest that the subse nsitivity to imipramine observed in Wistar-Kyoto rats: (i) can not be primarily explained by pharmacokinetic differences, and (ii) does not appear to be related to the monoaminergic systems. Wistar-Kyoto rats m ight be therefore not only a good animal model of depressive-like (pas sive) behavior, but also a model of resistance to antidepressants whic h could be used to investigate the neurobiological basis of such resis tance, which is also observed in some depressed patients. (C) 1997 Els evier Science B.V.