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Potential anxiolytic properties of 8-hydroxy-2-(Di-N-propylamino)tetralin, a selective serotonin1A receptor agonist

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Abstract

The effects of a selective serotonin1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in two animal models of anxiety. Peripherally injected 8-OH-DPAT in doses ranging from 0.125 to 2.0 mg/kg did not increase black-white transitions (BWT) and black square entries (BSE) in a two-compartment exploratory test or punished responding in a test of conditioned suppression of drinking. With 2.0 mg/kg 8-OH-DPAT BSE and unpunished responding were reduced. In an investigation of the drinking time of water-deprived rats, naive or habituated to the test environment, 1.0 and 2.0 mg/kg 8-OH-DPAT increased the drinking time of naive rats but 2.0 mg/kg 8-OH-DPAT reduced that of habituated animals. In animals deprived of water for 48 h or subjected to immobilization stress for 2 h, 1.0 mg/kg 8-OH-DPAT increased BWT and BSE values in the two-compartment exploratory test. Infusions of 5 μg/0.5 μl 8-OH-DPAT in the nucleus raphe medianus increased BWT and BSE values in the exploratory test and punished responding in the test of conditioned suppression of drinking, whereas the same dose of 8-OH-DPAT injected in the nucleus raphe dorsalis had no effect on punished but suppressed unpunished responding. The effects of 8-OH-DPAT are only detectable in the appropriate experimental conditions. When injected systemically, the effects are evident when a state of arousal of the animals contributes to the overall behavioural output. 8-OH-DPAT shows effects comparable to those of established anxiolytics such as benzodiazepines and barbiturates when it is injected in the nucleus raphe medianus, but not in the dorsalis. The data support the hypothesis that brain serotonin is involved in the mechanisms mediating behavioural suppression in the presence of aversive stimuli.

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References

  • Arvidsson LE, Hacksell U, Nilsson JLG, Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H (1981) 8-Hydroxy-2-(di-n-propylamino) tetralin, a new centrally acting 5-HT receptor agonist. J Med Chem 24:921–923

    Google Scholar 

  • Bendotti C, Samanin R (1986) 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicits eating in free feeding rats by acting on central serotonin neurons. Eur J Pharmacol 121:147–150

    Google Scholar 

  • Carli M, Samanin R (1982) Evidence that agents increasing water consumption do not necessarily generate “false positives” in conflict procedures using water as a reinforcer. Pharmacol Biochem Behav 17:1–3

    Google Scholar 

  • Carli M, Ballabio M, Caccia S, Garattini S, Samanin R (1981) Studies on some pharmacological activities of 7-nitro-2-amino-5-phenyl-3H-1,5-benzodiazepine (CP 1414 S) in the rat. A comparison with diazepam. Arzneimittelforschung 31:1721–1723

    Google Scholar 

  • Clarke A, File SE (1982) Selective neurotoxin lesions of the lateral septum: Changes in social and aggressive behaviours. Pharmacol Biochem Behav 17:623–628

    Google Scholar 

  • Crawley JN (1981) Neuropharmacologic specificity of a simple animal model for the behavioural actions of benzodiazepines. Pharmacol Biochem Behav 15:695–699

    Google Scholar 

  • Curzon G, Dourish CT, Kennett GA (1986) The 5-HT agonist 8-OH-DPAT attenuates stress-induced deficits in open field activity and feeding behaviour. Br J Pharmacol 87:20P

    Google Scholar 

  • Dourish CT, Hutson PH, Curzon G (1985) Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology 86:197–204

    Google Scholar 

  • Dourish CT, Hutson PH, Kennett GA, Curzon G (1986) 8-OH-DPAT-induced hyperphagia: Its neural basis and possible therapeutic relevance. Appetite [Suppl] 7:127–140

    Google Scholar 

  • Engel JA, Hjorth S, Svensson K, Carlsson A, Liljequist S (1984) Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol 105:365–368

    Google Scholar 

  • File SE, Hyde JRG, Macleod NK (1979) 5,7-Dihydroxytryptamine lesions of dorsal and median raphé nuclei and performance in the social interaction test of anxiety and in a home-cage aggression test. J Affective Disord 1:115–122

    Google Scholar 

  • Graeff FG (1974) Tryptamine antagonists and punished behavior. J Pharmacol Exp Ther 189:344–350

    Google Scholar 

  • Graeff FG, Schoenfeld RI (1970) Tryptaminergic mechanisms in punished and nonpunished behavior. J Pharmacol Exp Ther 173:277–283

    Google Scholar 

  • Goldberg HL, Finnerty RJ (1979) The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136:1184–1187

    Google Scholar 

  • Haigler HJ, Aghajanian SK (1977) Serotonin receptors in the brain. Fed Proc 36:2159–2164

    Google Scholar 

  • Hamon M, Cossery J-M, Spampinato U, Gozlan H (1986) Are there selective ligands for 5-HT1A and 5-HT1B receptor binding sites in brain? TIPS 7:336–338

    Google Scholar 

  • Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H, Arvidsson LE, Hacksell U, Nilsson JLG (1982) 8-Hydroxy-2-(di-n-propylamino) tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT receptor stimulating activity. J Neural Transm 55:169–188

    Google Scholar 

  • Hutson PH, Dourish CT, Curzon G (1986) Neurochemical and behavioural evidence for mediation of the hyperphagic action of 8-OH-DPAT by 5-HT cell body autoreceptors. Eur J Pharmacol 129:347–352

    Google Scholar 

  • Joseph MH, Kennett GA (1983) Stress-induced release of 5-HT in the hippocampus and its dependence on increased tryptophan availability: An in vivo electrochemical study. Brain Res 270:251–257

    Google Scholar 

  • Kantak KM, Wayner MJ, Stein JM (1978) Effects of various periods of food deprivation on serotonin turnover in the lateral hypothalamus. Pharmacol Biochem Behav 9:529–534

    Google Scholar 

  • Kennett GA, Dourish CT, Curzon G (1987) Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol 134:265–274

    Google Scholar 

  • Kilts CD, Commissaris RL, Rech RH (1981) Comparison of anticonflict drug effects on three experimental animal models of anxiety. Psychopharmacology 74:290–296

    Google Scholar 

  • Kilts CD, Commissaris RL, Cordon JJ, Rech RH (1982) Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam. Psychopharmacology 78:156–164

    Google Scholar 

  • König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams & Wilkins, Baltimore

    Google Scholar 

  • Linton M, Gallo PS (1975) The practical statistician. Brooks/Cole, Monterey, CA

    Google Scholar 

  • Mattila MJ, Aranko K, Seppala T (1982) Acute effects of buspirone and alcohol on psychomotor skills. J Clin Psychiatry 43:12 (Sec 2) 56–60

    Google Scholar 

  • Merlo Pich E, Samanin R (1986) Disinhibitory effects of buspirone and low doses of sulpiride and haloperidol in two experimental anxiety models in rats: Possible role of dopamine. Psychopharmacology 89:125–130

    Google Scholar 

  • Middlemiss DN, Fozard JR (1983) 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 90:151–153

    Google Scholar 

  • Patel JB, Malick JB (1980) Effects of isoproterenol and chlordiazepoxide on drinking and conflict behaviors in rats. Pharmacol Biochem Behav 12:819–821

    Google Scholar 

  • Rickels K, Weisman K, Norstad N, Singer M, Stoltz D, Brown A, Danton J (1982) Buspirone and diazepam in anxiety: A controlled study. J Clin Psychiatry 43:12 (Sec 2) 81–86

    Google Scholar 

  • Robichaud RC, Sledge KL (1969) The effects of p-chlorophenyl alanine on experimentally induced conflict in the rat. Life Sci 8:965–969

    Google Scholar 

  • Samanin R (1983) Drugs affecting serotonin and feeding. In: Curtis-Prior PB (ed) Biochemical pharmacology of obesity. Elsevier, Amsterdam, pp 339–356

    Google Scholar 

  • Schweizer EE, Amsterdam J, Rickels K, Kaplan M, Droba M (1986) Open trial of buspirone in the treatment of major depressive disorder. Psychopharmacol Bull 22:183–185

    Google Scholar 

  • Steinbusch HWM, Nieuwenhuys R (1983) The raphe nuclei of the rat brainstem: A cytoarchitectonic and immunohistochemical study. In: Emson PC (ed) Chemical neuroanatomy. Raven, New York, pp 131–207

    Google Scholar 

  • Thiébot M-H (1986) Are serotonergic neurons involved in the control of anxiety and the anxiolytic activity of benzodiazepines? Pharmacol Biochem Behav 24:1471–1477

    Google Scholar 

  • Thiébot M-H, Hamon M, Soubrié P (1983) The involvement of nigral serotonin innervation in the control of punishment-induced behavioural inhibition in rats. Pharmacol Biochem Behav 19:225–229

    Google Scholar 

  • Thiébot M-H, Soubrié P, Hamon M, Simon P (1984) Evidence against the involvement of serotonergic neurons in the antipunishment activity of diazepam in the rat. Psychopharmacology 82:355–359

    Google Scholar 

  • Tye NC, Everitt BJ, Iversen SD (1977) 5-Hydroxytryptamine and punishment. Nature 268:741–743

    Google Scholar 

  • Wolf G (1971) Elementary histology for neuropsychologist. In: Myers RD (ed) Methods in psychobiology, vol 1. Academic, London, pp 281–300

    Google Scholar 

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  1. Istituto di Ricerche Farmacologiche “Mario Negri”, via Eritrea 62, I-20157, Milan, Italy

    M. Carli & R. Samanin

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  1. M. Carli
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  2. R. Samanin
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Carli, M., Samanin, R. Potential anxiolytic properties of 8-hydroxy-2-(Di-N-propylamino)tetralin, a selective serotonin1A receptor agonist. Psychopharmacology 94, 84–91 (1988). https://doi.org/10.1007/BF00735886

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  • DOI: https://doi.org/10.1007/BF00735886

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