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?

Abstract

In three experiments we have studied the effects of acute administration 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-n-propylamino)tetralin (8-OH-DPAT), a selective 5HT1A receptor agonist, on behaviour of five 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 their activity in the holeboard and in the FST, the WKY rats being the most passive in both tests. The dose of 15 mg/kg DMI caused a profound inhibitory effect on locomotor/exploration activity in all strains. In the FST, this dose of DMI increased struggling and reduced immobility in BN, FIS and LEW rats, but did not exert any effect in SHR and WKY rats. 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 strains 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, both 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 very high dose of DMI (25 mg/kg). Hence, WKY rats are not only passive in the FST, but are also subsensitive to acute antidepressant administration. The present data indicate that the levels of activity of animals in the FST in drug-free conditions are not predictive of their response to antidepressants, and that inbred strains might be useful for studying the biological basis of subsensitivity to antidepressants and depressive-like behaviour.