Abstract
In the present study, the effects of a new anxiolytic, DN-2327, were compared to those of diazepam and buspirone in rats in the elevated plus-maze test. Two indices of anxiety were obtained in this test: the number of entries into the open arms expressed as a percentage of the total number of arm entries and the percentage of time spent on the open arms. Both a typical anxiolytic, diazepam, at 2.5, 5 and 10 mg/kg, PO and a new anxiolytic, DN-2327, at 2.5 and 5 mg/kg, PO dose-dependently increased the two indices: the percentage of time spent on the open arms and the percentage of open-arm entries. On the other hand, pentylenetetrazol (PTZ) at 10 and 20 mg/kg, IP decreased the two indices dose dependently as did yohimbine at 1.5 and 3 mg/kg, IP. DN-2327 at 2.5 and 5 mg/kg, PO and diazepam at 5 and 10 mg/kg, PO dose dependently and significantly increased the two indices that were suppressed following administration of PTZ at 10 mg/kg, IP. The effects of both DN-2327, 5 mg/kg, PO, and diazepam, 10 mg/kg, PO, on the two indices were significantly antagonized by the benzodiazepine (BZD) receptor antagonist flumazenil, 20 mg/kg, IP. Buspirone (2.5–20 mg/kg, PO) did not affect either of the two responses but dose dependently decreased the number of rearings, although in the Vogel conflict test, the anti-conflict activity of buspirone was equipotent to that of diazepam and DN-2327 at the minimum effective dose (10 mg/kg, PO) of each drug. In conclusion, the present experiment revealed that the anxiolytic effect of DN-2327 in this test was clear, whereas buspirone showed no apparent effect.
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References
Broadhurst PL (1957) Determinants of emotionality in the rat. 1. Situational factors. Br J Psychol 48:1–12
Charney DS, Heninger GR, Redmond DE (1983) Yohimbine-induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci 33:19–29
Chopin P, Briley M (1987) Animal models of anxiety: the effect of compounds that modify 5-HT neurotransmission. TIPS 8:383–388
Cochran WG, Cox GM (1957) Experimental designs, 2nd edn. Wiley, New York
Critchley MAE, Handley SL (1987a) 5-HT1A ligand effects in the X-maze anxiety test. Br J Pharmacol 92:660P
Critchley MAE, Handley SL (1987b) Effects in the X-maze anxiety model of agents acting at 5-HT1 and 5-HT2 receptors. Psychopharmacology 93:502–506
File SE, Lister RG (1984) Do the reductions in social interaction produced by picrotoxin and pentylenetetrazole indicate anxiogenic actions? Neuropharmacology 23:793–796
File SE, Johnston AL, Pellow S (1987) Effects of compounds acting at CNS 5-hydroxytryptamine systems on anxiety in the rat. Br J Pharmacol 91:265P
Gammans RE, Mayol RF, Eison MS (1983) Concentration of buspirone and 1-pyrimidinyl-piperazine, a metabolite, in rat brain. Fed Proc 42:377
Geller I, Seifter J (1960) The effects of meprobamate, barbiturates,d-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492
Goa KL, Ward A (1986) Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 32:114–129
Gower AJ (1986) In vivo α2-adrenoceptor antagonist activity of buspirone and its metabolite 1-(2-pyrimidyl)piperazine (1-PP) in the rat. Br J Pharmacol 89:726P
Hall CS (1934) Emotional behavior in the rat. I. Defecation and urination as measures of individual differences in emotionality. J Comp Psychol 18:385–403
Handley SL, Mithani S (1984) Effects on punished responding of drugs acting at alpha-adrenoceptors. Br J Pharmacol 82:341
Johnston AL, File SE (1989) Yohimbine's anxiogenic action: evidence for noradrenergic and dopaminergic sites. Pharmacol Biochem Behav 32:151–156
Lister RG (1985) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185
Moser PC (1989) An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology 99:48–53
Moser PC, Hibert M, Middlemiss DN, Mir AK, Tricklebank MD, Fozard JR (1988) Effects of MDL73005EF in animal models predictive of anxiolytic activity. Br J Pharmacol 93:3P
Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529
Pellow S, Chopin P, File SE, Briley M (1985a) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167
Pellow S, Chopin P, File SE (1985b) Are the anxiogenic effects of yohimbine mediated by its action at benzodiazepine receptors? Neurosci Lett 55:5–9
Pellow S, Johnston AL, File SE (1987) Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG7142 using the elevated plus-maze test in the rat. J Pharm Pharmacol 39:917–928
Peroutka S (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979
Prado de Carvaiho L, Venault P, Possier J, Chapouthier G (1983) Anxiogenic properties of convulsive agents. Soc Neurosci Abstr 9:128
Rodin EA, Calhoun HD (1970) Metrazol tolerance in a ‘normal’ volunteer population. J Nerv Ment Dis 150:438–450
Russell PA (1973) Relationships between exploratory behaviour and fear: a review. Br J Psychol 64:417–433
Van der Poel AM (1979) A note on “stretched attention”, a behavioural element indicative of an approach-avoidance conflict in rats. Anim Behav 27:446–450
Vogel RJ, Beer B, Clody DE (1971) A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacologia 21:1–7
Wada T, Fukuda N (1991) Pharmacologic profile of a new anxiolytic, DN-2327: effect of Ro15-1788 and interaction with diazepam in rodents. Psychopharmacology 103:314–322
Wada T, Nakajima R, Kurihara E, Narumi S, Masuoka Y, Goto G, Saji Y, Fukuda N (1989) Pharmacologic characterization of a novel non-benzodiazepine selective anxiolytic, DN-2327. Jpn J Pharmacol 49:337–349
Weissman BA, Barrett JE, Brady LS, Witkin JM, Mendelson WB, Paul SM, Skolnick P (1984) Behavioral and neurochemical studies on the anticonflict actions of buspirone. Drug Dev Res 4:83–93
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Wada, T., Fukuda, N. Effects of DN-2327, a new anxiolytic, diazepam and buspirone on exploratory activity of the rat in an elevated plus-maze. Psychopharmacology 104, 444–450 (1991). https://doi.org/10.1007/BF02245647
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DOI: https://doi.org/10.1007/BF02245647