DIFFERENTIAL RESPONSIVENESS OF INBRED STRAINS OF RATS TO ANTIDEPRESSANTS IN THE FORCED SWIMMING TEST - ARE WISTAR-KYOTO RATS AN ANIMAL-MODEL OF SUBSENSITIVITY TO ANTIDEPRESSANTS

In three experiments we have studied the effects of acute administrati on of various doses (5, 10, 15 and 25 mg/kg) of desipramine (DMI) and two doses (0.5 and 2 mg/kg) of 8-hydroxy-2-(di-M-propylamino)tetralin (8-OH-DPAT), a selective 5HT(1A) receptor agonist, on behaviour of fiv e inbred strains of rats in the holeboard and the forced swimming test (FST). The strains were Brown-Norway (BN), Fischer 344 (FIS), Lewis ( LEW), Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto (WKY). In drug-free conditions, the strains showed striking differences in thei r activity in the holeboard and in the FST, the WKY rats being the mos t passive in both tests. The dose of 15 mg/kg DMI caused a profound in hibitory effect on locomotor/exploration activity in all strains. In t he FST, this dose of DMI increased struggling and reduced immobility i n BN, FIS and LEW rats, but did not exert any effect in SHR and WKY ra ts. The lack of marked strain-dependent differences in the sensitivity to the inhibitory effects of DMI on locomotor activity or exploration rule out a major role of changes in the metabolism of drug among stra ins as an explanation for differential response to DMI in the FST. In further experiments three strains were used: BN (responsive), WKY (non -responsive) and the outbred Sprague Dawley (SD) rats. In the FST, bot h DMI and 8-OH-DPAT, at all doses, decreased immobility and increased struggling in BN and SD rats. However, WKY rats responded only to a ve ry high dose of DMI (25 mg/kg). Hence, WKY rats are not only passive i n the FST, but are also subsensitive to acute antidepressant administr ation. The present data indicate that the levels of activity of animal s in the FST in drug-free conditions are not predictive of their respo nse to antidepressants, and that inbred strains might be useful for st udying the biological basis of subsensitivity to antidepressants and d epressive-like behaviour.