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.

Depressive-like behavior and stress reactivity are independent traits in a Wistar Kyoto × Fisher 344 cross

“…18,[23][24][25][26][27]31,33 Their behavior in the FST and several other behavioral tests provide strong evidence that WKY rats are in a depressive-like state. While both WKY and F344 females exhibit high levels of immobility, WKY females did exhibit decreased climbing in the FST relative to F344 females.…”

“…5 The Wistar Kyoto (WKY) rat exhibits depressivelike behavior in a number of behavioral tests. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Among the behavioral tests that indicate a depressivelike state in the WKY, we chose to work with the forced swim test (FST), a measure frequently used to test for antidepressant drugs. This test is used in animal models to test for 'behavioral despair' [35][36][37][38] and/or 'passive coping behavior'.…”

Strain Differences in the Behavioral Effects of Antidepressant Drugs in the Rat Forced Swimming Test

“…However, these results disagree with those of Lahmame, Armario, and associates. These investigators reported that WKY rats were subsensitive in their response to the acute administration of desipramine or imipramine in the FST, although they did respond to chronic treatment with imipramine (15 mg/kg, once daily for 14 days) (Lahmame and Armario 1996;Lahmame et al 1997). A number of procedural differences might contribute to the discrepant results between Lahmame and those of Paré and ourselves, although both laboratories use FST scoring procedures that measure active behaviors.…”

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

“…It this context, it is noteworthy that on acute, but not repeated administration, WKY rats are resistant to the anti-immobility effect of the nonselective 5-HT reuptake inhibitor, imipramine, in the forced swim test (Lahmame et al 1997). In the latter case, serotonergic, but also noradrenergic systems may be involved as WKY rats (and SHRs) are resistant to the antiimmobility effect of the noradrenaline reuptake inhibitor desipramine (Lahmame and Armario 1996). In the present study, the possibility that the resistance of WKY rats to citalopram-elicited hypolocomotion involves the failure of the drug to reach serotonergic neurones and/ or to inhibit 5-HT reuptake was then examined.…”