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.
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References
Armario A, Gavaldà A, Martí O (1988) Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behaviour, swimming, immobility and defecation rate. Eur J Pharmacol 158:207–212.
Armario A, Gil M, Martí J, Pol O, Balasch J (1991) Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test. Pharmacol Biochem Behav 39:373–377
Armario A, Gavaldà A, Martí J (1995) Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology (In press)
Borsini F, Voltera G, Meli A (1986) Does the behavioural “despair” test measure “despair”? Physiol Behav 38:385–386
Cervo L, Samanin R (1991) Effect of chronic treatment with 8-OH-DPAT in the forced swimming test requires the integrity of presynaptic serotonergic mechanisms. Psychopharmacology 103:524–528
Cervo L, Grignaschi G, Samanin R (1988a) Differential effects of intracerebral and systemic administration of buspirone in the forced swimming test: involvement of a metabolite. Life Sci 43:2095–2102
Cervo L, Grignaschi G, Samanin R (1988b) 8-Hydroxy-2(di-n-propylanimo)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis. Eur J Pharmacol 158:53–59
Chojnacka-Wójcik E, Tatarczynska E, Golembiowska K, Przegalinskil (1991) Involvement of 5-HT1A receptors in the antidepressant-like activity of gepirone in the forced swimming test in rats. Neuropharmacology 30:711–717
File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacology 44:53–59
García-Márquez C, Armario A (1987a) Chronic stress depresses exploratory activity and behavioural performance in the forced swimming test without altering ACTH response to a novel acute stressor. Physiol Behav 40:33–38
García-Márquez C, Armario A (1987b) Interaction between chronic stress and clomipramine treatment in rats. Effects on exploratory activity, behavioural despair, and pituitary-adrenal function. Psychopharmacology 93:77–81
Gil M, Martí J, Armario A (1992) Inhibition of catecholamine synthesis depresses behaviour of rats in holeboard and forced swimming tests: influence of previous chronic stress. Pharmacol Biochem Behav 43:597–601
Graeff E O, Hunziker M H L, Graeff F G (1989) Effects of ipsapirone and BAY R 1531 on learned helplessness. Brazil J Med Biol Res 22:1141–1144
Glowa JR, Sternberg EM, Gold PW (1992) Differential behavioural response in LEW/N and F344/N rats: effects of corticotropin releasing hormone. Prog Neuro psychopharmacol Biol Psychiatry 16:549–560
Guitart X, Kogan JH, Berhow M, Terwilliger RZ, Aghajanian GK, Nestler EJ (1993) Lewis and Fisher rat strains display differences in biochemical, electrophysiological and behavioural parameters: satudies in the nucleus accumbens and locus coeruleus of drug naive and morphine-treated animals. Brain Res 611:7–17
Kasahara K, Nagatani T, Takao K, Hashimoto S (1993) Role of 5-HT1A receptors in the forced swimming wheel test in reserpine-treated mice. Life Sci 52:1741–1749
Kostowski W, Dyr W, Krzascik P, Järbe T, Archer T (1992) 5-Hydroxytryptamine1A receptor agonists in animal models of depression and anxiety. Pharmacol Toxicol 71:24–30
Leaton R, Cassella JV (1983) Locomotor activity, auditory startle and shockholds in spontaneously hypertensive rats. Physiol Behav 31:103–109
Martí J, Armario A (1993) Effects of diazepam and desipramine in the forced swimming test: influence of previous experience with situation. Eur J Pharmacol 236:295–299
Martí J, Armario A (1995) Forced swimming test behaviour is not related to the corticosterone levels achieved in the test. A study with four inbred rat strains. Physiol Behav (In press)
McCarty R, Kopin I (1978) Sympatho-adrenal medullary activity and behavior during exposure to footshock stress: a comparison of seven rat strains. Physiol Behav 21:567–572
McCarty R, Kirby RF (1982) Spontaneous hypertensive and openfield behavior. Behav Neural Biol 34:450–452
Nikulina EM, Skrinskaya JA, Popova NK (1991) Role of genotype and dopamine receptors in behavior of inbred mice in a forced swimming test. Psychopharmacology 105:525–529
Nishimura H, Ida Y, Tsuda A, Tanaka M (1989) Opposite effects of diazepam and b-CCE on immobility and straw-climbing behaviour of rats in a modified forced-swim test. Pharmacol Biochem Behav 33:227–231
Nomura S, Shimizu, Kinjo M, Kametani H, Nakazawa T (1982) A new behavioral test for antidepressant drugs. Eur J Pharmacol 83:171–175
Paré WP (1989a) “Behavioural despair” test predicts stress ulcer in WKY rats. Physiol Behav 46:483–487
Paré WP (1989b) Stress ulcer susceptibility and depression in Wistar Kyoto (WKY) rats. Physiol Behav 46:993–998
Paré WP (1992) The performance of WKY rats on three tests of emotional behavior. Physiol Behav 51:1051–1056
Pol O, Campmany L, Gil M, Armario A (1992) Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization. Pharmacol Biochem Behav 42:407–412
Porsolt RD, Bertin A, Jalfre M (1977a) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336
Porsolt RD, LePichon M, Jalfre M (1977b) Depression: a new animal model sensitive to antidepressant treatment. Nature 266:730–732
Porsolt RD, Anton G, Blavet N, Jalfre M (1978a) Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391
Porsolt RD, Bertin A, Jalfre M (1978b) Behavioral despair in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294
Schiller GD, Pucilowski O, Wienicke C, Overstreet DH (1992) Immobility-reducing effects of antidepressants in a genetic animal model of depression. Brain Res Bull 28:821–823
Schreiber R, De Vry J (1993) Neuroanatomical basis for the antidepressant-like effects of the 5-TH1Areceptor agonists 8-OH-DPAT and ipsapirone in the forced swimming test. Behav Pharmacol 4:625–636
Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370
Trullas R, Jackson B, Skolnick P (1989) Genetic differences in a tail suspension test for evaluating antidepressant activity. Psychopharmacology 99:287–288
Van der Heyden JAM, Molewijk, Olivier B (1987) Strain differences in response to drugs in the tail suspension test for antidepressant activity. Psychopharmacology 92:127–130
Weiss JM, Goodman PA, Losito BG, Corrigan S, Charry JM, Bailey W H (1981) Behavioural depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Res Rev 3:167–205
Willner P (1984) The validity of animal models of depression. Psychopharmacology 83:1–16
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Lahmame, A., Armario, A. 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?. Psychopharmacology 123, 191–198 (1996). https://doi.org/10.1007/BF02246177
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DOI: https://doi.org/10.1007/BF02246177