Abstract
Exposure of male Wistar rats to one single session of ten inescapable footshocks induces changes in the behavioural responses to environmental stimuli as measured in the “noise test” 14 days later. Shocked (S) rats showed decreased locomotion and rearing during the first 3 min of exposure to a novel environment compared to control (C) rats. When the 85 dB background noise was switched off a marked immobility response emerged in S rats, concomitant with a further decrease in locomotion and rearing. In response to noise off, C rats showed hardly any immobility and a much smaller reduction in locomotion and rearing compared to S rats. These long-lasting changes in behaviour were not reversed by acute treatment with the antidepressants fluvoxamine (3.0–30.0 mg/kg) and desmethylimipramine (DMI, 2.5–10.0 mg/kg) injected IP 30 min before the noise test on day 14 following the shock session. Chronic treatment (day 1 to day 14) with flvoxamine or DMI did not reverse the behavioural deficits induced by shock exposure. Diazepam (0.6–5.0 mg/kg) administered acutely only reversed the effects of shock on locomotion during the first 3 min of the noise test. Chronic treatment with diazepam normalized the shock-induced decrease in locomotion and attenuated the rearing decrease during the first 3 min of the test, and partially restored shock-induced changes in behavioural response to switching off the noise. The most potent drug in this study was the 5-HT1A receptor agonist flesinoxan (0.3–3.0 mg/kg). Both acute and chronic drug treatment were equally effective in reversing the shock-induced locomotion deficits as well as the marked immobility response in S rats, although rearing was not reversed. However, flesinoxan also increased locomotion and reduced rearing in C rats, suggesting some nonspecific stimulating effects of flesinoxan. In conclusion, the footshock-induced long-lasting behavioural changes are sensitive to treatment with (putative) anxiolytic agents, whereas no beneficial effect of the antidepressant drugs was found.
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References
Ahlenius S, Larsson K, Wijkström A (1991) Behavioral and biochemical effects of the 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT in the rat. Eur J Pharmacol 200:259–266
Anderson DC, Crowell C, Lupo JV (1976) Different intensities of unsignalled inescapable shock treatment as determinants of non-shock-motivated open field behaviour: A resolution of disparate results. Physiol Behav 17:391–394
Angst J, Vollrath M (1991) The natural history of anxiety disorders. Acta Psychiatr Scand 84:446–452
Anisman H, Zacharcko RM (1982) Depression: the predisposing influence of stress. Behav Brain Sci 5:89–137
Antelman SM (1988) Time-dependent sensitization as the cornerstone for a new approach to pharmacotherapy: drugs as foreign/stressful stimuli. Drug Dev Res 14:1–30
Antelman SM, Eichler AJ, Black CA, Kocan D (1980) Interchangeability of stress and amphetamine in sensitization. Science 207:329–331
Antelman SM, Knopf S, Kocan D, Edwards DJ, Ritchie JC, Nemeroff CB (1988) One stressful event blocks multiple actions of diazepam up to at least a month. Brain Res 445:380–385
Archer J (1973) Tests for emotionality in rats and mice: a review. Anim Behav 21:205–235
Barrett JE, Gleeson S, Nader MA, Hoffman SM (1989) Anticonflict effects of the 5-HT1A compound flesinoxan. J Psychopharmacol 3:64–69
Bauman RA, Kant GJ (1991) Circadian effects of escapable and inescapable shock on food intake and wheelrunning of rats. Physiol Behav 51:167–174
Berendsen HHG, Jenck F, Broekkamp CLE (1989) Selective activation of 5-HT1A receptors induces lower lip retraction in the rat. Pharmacol Biochem Behav 33:821–827
Blanchard DC, Blanchard RJ (1988) Ethoexperimental approaches to the biology of emotion. Annu Rev Psychol 39:43–68
Bolles RC (1970) Species-specific defense reactions and avoidance learning. Psychol Rev 77:32–48
Borison RL, Albrecht JW, Diamond BI (1990) Efficacy and safety of a putative anxiolytic agent: ipsapirone. Psychopharmacol Bull 26:207–211
Brunello N, Riva M, Volterra A, Racagni G (1986) Biochemical changes in rat brain after acute and chronic administration of fluvoxamine, a selective 5-HT uptake blocker: comparison with desmethylimipramine. Adv Pharmacother 2:189–196
De Jonghe F, Swinkels J, Tuynman-Qua H (1991) Randomized double-blind study of fluvoxamine and maprotiline in treatment of depression. Pharmacopsychiatry 24:21–27
Desan PH, Silbert LH, Maier SF (1988) Long-term effects of inescapable stress on daily running activity and antagonism by desipramine. Pharmacol Biochem Behav 30:21–29
DSM-IIIR (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, revised. American Psychiatric Association, Washington, DC
File SE (1985a) What can be learned from the effects of benzodiazepines on exploratory behavior? Neurosci Biobehav Rev 9:45–54
File SE (1985b) Tolerance to the behavioural actions of benzodiazepines. Neurosci Biobehav Rev 9:113–121
File SE, Tucker JC (1986) Behavioral consequences of antidepressant treatment in rodents. Neurosci Biobehav Rev 10:123–134
Glazer HI, Weiss JM (1976a) Long-term and transitory effects. J Exp Psychol [Anim Behav Proc] 2:191–201
Glazer HI, Weiss JM (1976b) Long-term interference effect: an alternative to “learned helplessness”. J Exp Psychol [Anim Behav Proc] 2:202–213
Goa KL, Ward A (1986) Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 32:114–129
Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (part two). N Engl J Med 319:413–420
Jesberger JA, Richardson JS (1985) Animal models of depression: parallels and correlates to severe depression in humans. Biol Psychiatry 20:764–784
Katz RJ (1982) Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol Biochem Behav 16:965–968
Katz RJ, Baldrighi GA (1982) Further parametric study of imipramine in an animal model of depression. Pharmacol Biochem Behav 16:969–972
Katz RJ, Sibel M (1982) Further analysis of the specificity of a novel animal model of depression—effects of an antihistaminic, antipsychotic and anxiolytic compound. Pharmacol Biochem Behav 16:979–982
Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–251
Koolhaas JM, Hermann PM, Kemperman C, Bohus B, Van den Hoofdakker RH, Beersma DGM (1990) Single social defeat in male rats induces a gradual but long-lasting behavioural change: a model of depression? Neurosci Res Commun 7:35–41
Levine S, Madden J, Conner RL, Moskal JR, Anderson DC (1973) Physiological and behavioral effects of prior aversive stimulation (preshock) in the rats. Physiol Behav 10:467–471
Lister RG (1990) Ethologically-based animal models of anxiety disorders. Pharmacol Ther 46:321–340
Margules DL, Stein L (1968) Increase of “antianxiety” activity and tolerance of behavioral depression during chronic administration of oxazepam. Psychopharmacologia 13:74–80
Mizcek KA, Thompson ML, Tornatzky W (1991) Subordinate animals: behavioral and physiological adaptations and opioid tolerance. In: Brown MR, Rivier C, Koob G (eds) Neurobiology and neuroendocrinology of stress. Marcel Dekker, New York
Mos J, Olivier B (1989) Ultrasonic vocalizations by rat pups as an animal model for anxiolytic activity: effects of serotonergic drugs. In: Bevan P, Cools AR, Archer T (eds) Behavioural pharmacology of 5-HT. Lawrence Erlbaum, New Jersey, pp 361–369
Murua VS, Gomez RA, Andrea ME, Molina VA (1991) Shuttlebox deficits induced by chronic variable stress: reversal by imipramine administration. Pharmacol Biochem Behav 38:125–130
Ottenweller JE, Natelson BH, Pitman DL, Drastal SD (1989) Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness. Biol Psychiatry 26:829–841
Rodgers RJ, Shepherd JK (1992) Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend on treatment regimen and prior maze experience. Psychopharmacology 106:102–110
Rodríguez-Echandía E.L, Gonzalez AS, Cabrera R, Fracchia LN (1988) A further analysis of behavioral and endocrine effects of unpredictable chronic stress. Physiol Behav 43:789–795
Schipper J, Tulp MTM, Berkelmans B, Mos J, Van der Heyden JAM, Olivier B (1991) Preclinical pharmacology of flesinoxan: a potential anxiolytic and antidepressant drug. Hum Psychopharmacol Clin Exp 6:S53-S61
Seligman MEP, Roselini RA, Kozak MJ (1975) Learned helplessness in the rat: time course, immunization, and reversibility. J Comp Physiol Psychol 88:542–547
Smith LM, Peroutka SJ (1986) Differential effects of 5-hydroxytryptamine1A selective drugs on the 5-HT behavioral syndrome. Pharmacol Biochem Behav 24:1513–1519
Soubrié P (1989) 5-HT1A receptors: a bridge between anxiety and depression? In: Bevan P, Cools AR, Archer T (eds) Behavioural pharmacology of 5-HT. Lawrence Erlbaum, New Jersey, pp 337–352
Timmermans PJA (1978) Social behaviour in the rat. Thesis, Nijmegen, The Netherlands
Tricklebank MD, Forler C, Fozard JR (1985) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propyl-amino) tetralin in the rat. Eur J Pharmacol 106:271–282
Tucker JC, File SE (1986) The effects of tricyclic and “atypical” antidepressants on spontaneous locomotor activity in rodents. Neurosci Biobehav Rev 10:115–121
Van Dijken HH, Van der Heyden JAM, Mos J, Tilders FJH (1991) Long-lasting behavioural changes after a single footshock stress session. A model of depression? In: Olivier B, Mos J, Slangen JL (eds) Animal models in psychopharmacology. Birkhäuser, Basel, pp 231–236
Van Dijken HH, Mos J, Tulp MThM, Tilders FJH (1992a) Long-lasting effects of a single footshock session on behavioural and endocrine responsiveness in male rats. In: Kvetnansky R, McCarty R, Axelrod J (eds) Stress: neuroendocrine and molecular approaches. Gordon and Breach, New York, pp 473–480
Van Dijken HH, Van der Heyden JAM, Mos J, Tilders FJH (1992b) Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats. Physiol Behav 51:787–794
Van Dijken HH, Mos J, Van der Heyden JAM, Tilders FJH (1992c) Characterization of stress-induced long-term behavioural change in rats: evidence in favor of anxiety. Physiol Behav (in press)
Von Bardeleben U, Holsboer F (1988) Human corticotropin releasing hormone: Clinical studies in patients with affective disorders, alcoholism, panic disorder and in normal controls. Prog Neuropsychopharmacol Biol Psychiatry 12:S165-S187
Willner P (1990) Animal models of depression: an overview. Pharmacol Ther 45:425–455
Willner P, Towell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93:358–364
Zisook S, Shuchter SR (1991) Depression through the first year after the death of a spouse. Am J Psychiatry 148:1346–1352
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Van Dijken, H.H., Tilders, F.J.H., Olivier, B. et al. Effects of anxiolytic and antidepressant drugs on long-lasting behavioural deficits resulting from one short stress experience in male rats. Psychopharmacology 109, 395–402 (1992). https://doi.org/10.1007/BF02247714
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DOI: https://doi.org/10.1007/BF02247714