Abstract A fully automated version of the black and white two-compartment box for mice is presented. The anxiolyticlike effects of the benzodiazepines, diazepam and chlordiazepoxide, were confirmed, and the involvement of serotonergic mechanisms was studied in this animal model of anxiety. The partial 5-HT_1A receptor agonists, buspirone and ipsapirone showed anxiolytic-like effects in a limited dose interval. The full agonist hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) was inactive. The non-selective 5-HT₁ receptor agonist, eltoprazine, induced marked increases of exploratory behaviour in the white compartment over a broad range of doses. Also pindolol a mixed 5-HT_1A/1B and β-adrenergic receptor antagonist showed anxiolytic-like effects, whereas another compound with a similar profile (-)-, penbutolol and the β-adrenoceptor antagonist ICI 118,551, was inactive. The 5-HT_2A/2C receptor antagonist, ritanserin, showed anxiogenic-like, and the 5-HT₃ receptor antagonists, zacopride and ondansetron, showed anixiolytic-like effects. An overall increase of serotonergic activity by means of 5-HT uptake inhibition (citalopram), 5-HT release (fenfluramine) or administration of a 5-HT precursor (1–5-HTP) facilitated exploratory activity in the white compartment. Reduction of serotonergic activity by treatment with the 5-HT depletor p-chloro-phenylalanine methyl ester (PCPA) did not change the exploratory behaviour, but attenuated the response to fenfluramine significantly.

References

Carli, M., C. Prontera & R. Saminin: Evidence that central 5-hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone. Brit. J. Pharmacol. 1989, 96, 829–836.
10.1111/j.1476-5381.1989.tb11891.x
CAS PubMed Web of Science® Google Scholar
Chang, R. S. L. & V. J. Lotti: Characterization of β-adrenergic receptors in the rat vas deferens using [³H]-dihydroalprenolol binding. Life Sci. 1983, 32, 2603–2609.
10.1016/0024-3205(83)90245-X
CAS PubMed Web of Science® Google Scholar
Cheng, H.K., B. Costall, M. E. Kelly & R. J. Naylor: Actions of 5-hydroxytryptophan to inhibit and disinhibit mouse behaviour in the light/dark test. Eur. J. Pharmacol. 1994, 255, 39–49.
10.1016/0014-2999(94)90080-9
CAS PubMed Web of Science® Google Scholar
Colpaert, F. C., T. F. Meert, C. J. E. Niemegeers & P. A. J. Janssen: Behavioral and 5-HT antagonist effects of ritanserin: A pure and selective antagonist of LSD discrimination in rat. Psychopharmacol. 1985, 86, 45–54.
10.1007/BF00431683
CAS PubMed Web of Science® Google Scholar
Costall B. & R. J. Naylor: The psychopharmacology of 5-HT₃ receptors. Pharmacol. Toxicol. 1992, 71, 401–415.
10.1111/j.1600-0773.1992.tb00570.x
CAS PubMed Web of Science® Google Scholar
Costall, B., M.E. Kelly, R. J. Naylor & E. S. Onaivi: Actions of buspirone in a putative model of anxiety in the mouse. J. Pharm. Pharmacol. 1988, 40, 494–500.
10.1111/j.2042-7158.1988.tb05284.x
CAS PubMed Web of Science® Google Scholar
Costall, B., B. J. Jones, M. E. Kelly, R. J. Naylor & D. M. Tomkins: Exploration of mice in a black and white test box: Validation as a model of anxiety. Pharmacol. Biochem. Behav. 1989, 32, 777–785.
10.1016/0091-3057(89)90033-6
CAS PubMed Web of Science® Google Scholar
Costain, D. W. & A. R. Green: β-adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine. Brit. J. Pharmacol. 1978, 64, 193–200.
10.1111/j.1476-5381.1978.tb17289.x
CAS PubMed Web of Science® Google Scholar
Crawley, J. N.: Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol. Biochem. Behav. 1981, 15, 695–699.
10.1016/0091-3057(81)90007-1
CAS PubMed Web of Science® Google Scholar
Crawley, J. N. & G. Davis: Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains. Brain Res. Bull. 1982, 8, 609–612.
10.1016/0361-9230(82)90087-9
CAS PubMed Web of Science® Google Scholar
Crawley, J. N. & F. K. Goodwin: Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 1980, 13, 167–170.
10.1016/0091-3057(80)90067-2
CAS PubMed Web of Science® Google Scholar
Graeff, F. G. Role of 5-HT in defensive behaviour and anxiety. Rev. Neurosci. 1993, 4, 181–211.
10.1515/REVNEURO.1993.4.2.181
PubMed Web of Science® Google Scholar
Griebel, G., M. Saffroy-Spittler, R. Misslin, E. Vogel & J. R. Martin: Serenics fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice. Psychopharmacol. 1990, 102, 498–502.
10.1007/BF02247131
CAS PubMed Web of Science® Google Scholar
Griebel G., J.-L. Moreau, F. Jenck, R. Mislin & J. R. Martin: Acute and chronic treatment with 5-HT reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents. Psychopharmacol. 1994, 113, 463–470.
10.1007/BF02245224
CAS PubMed Web of Science® Google Scholar
Hjorth, S.: (-)-Penbutolol as a blocker of central 5-HT_1A receptor-mediated responses. Eur. J. Pharmacol. 1992, 222, 121–127.
10.1016/0014-2999(92)90471-F
CAS PubMed Web of Science® Google Scholar
Hjorth, S. & A. Carlsson: Is pindolol a mixed agonist-antagonist at central serotonin (5-HT) receptors Eur. J. Pharmacol. 1986, 129, 131–138.
10.1016/0014-2999(86)90344-4
CAS PubMed Web of Science® Google Scholar
Hyttel, J., K.P. Bøgesø, J. Perregaard & C. Sánchez: The pharmacological effect of citalopram resides in the (S)-(+)-enantiomer. J. Neur. Transm. (Gen. Sect.) 1992, 88, 157–160.
10.1007/BF01244820
CAS PubMed Web of Science® Google Scholar
Kennett, G. A., P. Whitton, K. Shah & G. Curson: Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT_1C receptor antagonists. Eur. J. Pharmacol. 1989, 164, 445–454.
10.1016/0014-2999(89)90252-5
CAS PubMed Web of Science® Google Scholar
Kilfoil, T., A. Michel, D. Montgomery & R. L. Whiting: Effects of anxiolytic and anxiogenic drugs on exploratory activity in a simple model of anxiety in mice. Neuropharmacol. 1989, 28, 901–905.
10.1016/0028-3908(89)90188-3
CAS PubMed Web of Science® Google Scholar
Kshama, D., H. J. Hrishikeshavan, R. Shanbhogue & U.S. Munonyedi: Modulation of baseline behavior in rats by putative serotonergic agents in three ethoexperimental paradigms. Behav. Neur. Biol. 1990, 54, 234–253.
10.1016/0163-1047(90)90617-F
CAS PubMed Web of Science® Google Scholar
López-Rubalcava, C., A. Sáldivar & A. Fernández-Guasti: Interaction of GABA and serotonin in the anxiolytic action of diazepam and serotonergic anxiolytics. Pharmacol. Biochem. Behav. 1992, 43, 433–440.
10.1016/0091-3057(92)90173-D
CAS PubMed Web of Science® Google Scholar
Martin, P., P. Soubrié & P. Simon: Comparative study of the effects of stimulation or blockade of β-adrenoceptors on the headtwitches induced in mice by 5-hydroxytryptophan versus 5-methoxy-N, N-dimethyltryptamine. J. Pharmacol. 1986, 17, 119–125.
CAS PubMed Web of Science® Google Scholar
Middlemiss, D. N.: Blockade of the central 5-HT autoreceptor by β-adrenoceptor antagonists. Eur. J. Pharamacol. 1986, 120, 51–56.
10.1016/0014-2999(86)90638-2
CAS PubMed Web of Science® Google Scholar
Misslin, R., G. Griebel, M. Saffroy-Spittler & E. Vogel: Anxiolytic and sedative effects of 5-HT_1A ligands, 8-OH-DPAT and MDL 73005EF, in mice. NeuroRep. 1990, 1, 267–270.
10.1097/00001756-199011000-00025
CAS Google Scholar
O'Donnell, S. R. & J. C. Wanstall: Evidence that ICI 118,551 is a potent, highly β₂-selective adrenoceptor antagonist and can be used to characterize beta-adrenoceptor populations in tissues. Life Sci. 1980, 27, 671–677.
10.1016/0024-3205(80)90008-9
CAS PubMed Web of Science® Google Scholar
Onaivi, E. S. & B. R. Martin: Neuropharmacological and physiological validation of a computer-controlled two-compartment black and white box for the assessment of anxiety. Progr. Neuro-Psychopharmacol. Biol. Psychiat. 1989, 13, 963–976.
10.1016/0278-5846(89)90047-X
CAS PubMed Web of Science® Google Scholar
Perregaard, J., C. Sánchez & J. Arnt: Recent developments in anxiolytics. Curr. Opinion Ther. Pat. 1993, 3, 101–128.
10.1517/13543776.3.1.101
Google Scholar
Rodgers, R. J., J. C. Cole, M. R. Cobain, P. Daly, P. J. Doran, J. R. Eells & P. Wallis: Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze: profile comparisons with 8-OH-DPAT, CGS 12066B, TFMPP and mCPP. Behav. Pharmacol. 1992, 3, 621–634.
10.1097/00008877-199212000-00009
CAS PubMed Web of Science® Google Scholar
Sánchez, C.: Comparison of exploratory behaviour of rats and mice in a black and white test box. J. Psychopharmacol. Abst. Book BAP/EBPS Meeting. 1992 A73, abstract no. 289.
Google Scholar
Sánchez, C.: Effect of serotonergic drugs on footshock-induced ultrasonic vocalization in adult male rats. Behav. Pharmacol. 1993, 4, 269–277.
10.1097/00008877-199306000-00010
CAS PubMed Web of Science® Google Scholar
Sánchez, C., J. Arnt, J. Hyttel & E. K. Moltzen: The role of serotonergic mechanisms in inhibition of isolation-induced agression in male mice. Psychopharmacol. 1993, 110, 53–59.
10.1007/BF02246950
CAS PubMed Web of Science® Google Scholar
Sijbesma, H., J. Schipper & E. R. De Kloet: The anti-aggressive drug eltoprazine preferentially binds to 5-HT_1A and 5-HT_1B receptor subtypes in rat brain: sensitivity to guanine nucleotides. Eur. J. Pharmacol. 1990a, 187, 209–223.
10.1016/0014-2999(90)90008-T
CAS PubMed Web of Science® Google Scholar
Sijbesma, H., J. Schipper & E. R. De Kloet: Eltroprazine, a drug which reduces aggressive behaviour, binds selectively to 5-HT₁ receptor sites in the rat brain: an autoradiographic study. Eur. J. Pharmacol. 1990b, 177, 55–66.
10.1016/0014-2999(90)90549-L
CAS PubMed Web of Science® Google Scholar
Simiand, J., P. E. Keane, M. C. Barnouin, M. Keane, P. Soubrié & G. Le Fur: Neuropsycho pharmacological profile in rodents of SR 57746A, a new potent 5-HT_1A receptor agonist. Fundam. Clin. Pharmacol. 1993, 7, 413–427.
CAS PubMed Web of Science® Google Scholar
Young, R. & D. N. Johnson: A fully automated light/dark apparatus useful for comparing anxiolytic agents. Pharmacol Biochem. Behav. 1991, 40, 739–743.
10.1016/0091-3057(91)90078-G
CAS PubMed Web of Science® Google Scholar

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Volume77, Issue1

July 1995

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Serotonergic Mechanisms Involved in the Exploratory Behaviour of Mice in a Fully Automated Two-Compartment Black and White Test Box

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Serotonergic Mechanisms Involved in the Exploratory Behaviour of Mice in a Fully Automated Two-Compartment Black and White Test Box

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