Differential sensitivity to 8-hydroxy-2-(di-n-propylamino)tetralin-induced corticosterone secretion and hypothermia between Sprague-Dawley rats from different breeding colonies.
The sensitivity of Sprague-Dawley rats from 4 different breeding colonies (ALAB, M&B, B&K, Charles River) and one breeding colony of Wistar rat (M&B) to the 5-hydroxytryptamine1A (5-HT1A) receptor stimulatory effect of 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) resulting in corticosterone secretion and hypothermia was compared. The dose-response curves of the increase in plasma corticosterone showed that ALAB and M&B rats were 3.5 times more sensitive to 8-OH-DPAT than B&K and Charles River rats, the Wistar rats being in between. The attenuation of the corticosterone response 24 hr after a single injection of 1 mg/kg 8-OH-DPAT was greater for the ALAB and M&B rats than for B&K, Charles River and Wistar rats. The comparison of the 8-OH-DPAT-induced hypothermia in the various rat colonies showed a similar pattern: the sensitivity of ALAB rats was about twice that of M&B, B&K and Wistar rats, Charles River rats being 9 times less sensitive. The attenuation of the response 24 hr after 1 mg/kg 8-OH-DPAT measured as the shift in dose-response showed similar shift factors (4.1 to 6.7) for all rat colonies except for the B&K rats (3.0). The hypothermic response at 0.1 mg/kg 8-OH-DPAT was significantly lower for the Charles River and B&K rats than for the ALAB rats. Similarly was the maximal attenuation of the hypothermic effect in these rats less than half of that of the ALAB rats. The possible cause of the observed differences in the response to 8-OH-DPAT between these rat colonies is discussed in terms of receptor reserves and the involvement of other transmitter systems in the responses.
Kelder
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D
Bioscience, Local Discovery, AstraZeneca R & D Södertälje, Hedvägen 8, S-151 85 Södertälje, Sweden.
Ross
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SB
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone