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Neurochemical and behavioural studies with RU-24969 in the rat

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Abstract

The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.

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References

  • Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, Wikstrom H, Sanchez D, Arvidsson L-E, Hacksell U, Nilsson JLG (1981) Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 15:785–792

    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 121:149–150

    Google Scholar 

  • Benfenati F, Ferretti P, Ferretti C, Ponzio F, Algeri S (1982) Determination, of l-DOPA in brain tissue using high-performance liquid chromatography with electrochemical detection to study the activity of central dopaminergic neurones. IRCS Med Sci 10:425–426

    Google Scholar 

  • Borsini F, Nowakowska E, Samanin R (1984) Effect of repeated treatment with desipramine in the behavioural “despaire” test in rats: Antagonism by “atypical” but not “classical” neuroleptics or antiadrenergic drugs. Life Sci 34:1171–1176

    Google Scholar 

  • Borsini F, Pulvirenti L, Samanin R (1985) Evidence of dopamine involvement in the effect of repeated treatment with various antidepressants in the behavioural “despair” test in rats. Eur J Pharmacol 110:253–256

    Google Scholar 

  • Brazell MP, Marsden CA, Nisbet AP, Routledge C (1985) The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo. Br J Pharmacol 86:209–216

    Google Scholar 

  • Carlsson A (1974) Measurements of monoamine synthesis and turnover with special reference to 5-hydroxytryptamine. Adv Biochem Psychopharmacol 10:75–81

    Google Scholar 

  • Costall B, Naylor RJ, Marsden CD, Pycock CJ (1976) Serotoninergic modulation of the dopamine response from the nucleus accumbens. J Pharm Pharmacol 28:523–526

    Google Scholar 

  • Di Paolo T, Dupont A, Savard P, Daigle M (1983) Determination of 5-hydroxytryptophan, 5-hydroxytryptamine, and 5-hydroxyindolacetic acid in 20 rat brain nuclei using liquid chromatography with electrochemical detection. Can J Physiol Pharmacol 61:530–534

    Google Scholar 

  • Dourish CT, Hutson PH, Curzon G (1985) Low doses of 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 

  • Dray A, Davies J, Oakley NR, Tongroach P, Vellucci S (1978) The dorsal and median raphe projections to the substantia nigra in the rat: Electrophysiological, biochemical and behavioural observations. Brain Res 151:431–442

    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 

  • Engel G, Gothert M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch Pharmacol 332:1–7

    Google Scholar 

  • Euvrard C, Boissier JR (1980) Biochemical assessment of central 5-HT agonist activity of RU-24969 (a piperinidyl indole). Eur J Pharmacol 63:65–72

    Google Scholar 

  • Gardner CR (1986) Recent developments in 5HT-related pharmacology of animal models of anxiety. Pharmacol Biochem Behav 24:1479–1487

    Google Scholar 

  • Green AR, Guy AP, Gardner CR (1984) The behavioural effects of RU-24969, a suggested 5-HT1 receptor agonist in rodents and the effect on the behaviour of treatment with antidepressants. Neuropharmacology 23:655–661

    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, Engel JA, Carlsson A (1986) Anticonflict effects of low doses of the dopamine agonist apomorphine in the rat. Pharmacol Biochem Behav 24:237–240

    Google Scholar 

  • James TA, Starr MS (1980) Rotational behaviour elicited by 5-HT in the rat: Evidence for an inhibitory role of 5-HT in the substantia nigra and corpus striatum. J Pharm Pharmacol 32:196–200

    Google Scholar 

  • Johnston AL, File SE (1986) 5-HT and anxiety: Promises and pitfalls. Pharmacol Biochem Behav 24:1467–1470

    Google Scholar 

  • Kennett GA, Dourish C, Curzon G (1987) Antidepressant-like action of 5-HT1a agonists and conventional antidepressants in an animal model of depression. Eur J Pharmcol 134:265–274

    Google Scholar 

  • Leibowitz SF (1980) Neurochemical systems of the hypothalamus: Control of feeding and drinking behaviour and water-electrolyte excretion. In: Morgan PJ, Panksepp J (eds) Handbook of the hypothalamus, vol 1, part A. Behavioural studies of the hypothalamus. Dekker, New York, pp 299–347

    Google Scholar 

  • Maj J, Rogoz Z, Skuza G, Sowinska H (1984) Repeated treatment with antidepressant drugs potentiates the locomotor response to (+)-amphetamine. J Pharm Pharmacol 36:127–130

    Google Scholar 

  • Marsden CA, Martin KF (1985) RU-24969 decreases 5-HT release in the SCN by acting on 5-HT receptors in the SCN but not the dorsal raphe. Br J Pharmacol [Suppl] 85:219P

  • 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 (1985) The putative 5-HT1 receptor agonist, RU-24969, inhibits the efflux of 5-hydroxytryptamine from rat frontal cortex slices by stimulation of the 5-HT autoreceptor. J Pharm Pharmacol 37:434–437

    Google Scholar 

  • Middlemiss DN, Neill J, Tricklebank MD (1985) Subtypes of the 5-HT receptor involved in hypothermia and forepaw treading induced by 8-OPH-DPAT. Br J Pharmacol 85:251P

  • Oberlander C (1983) Effects of a potent 5-HT agonist, RU-24969, on the mesocorticolimbic and nigrostriatal dopamine systems. Br J Pharmacol 80:675P

    Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradigraphic maptping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230

    Google Scholar 

  • Pijnenburg AJJ, van Rossum JM (1973) Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003–1005

    Google Scholar 

  • Porsolt RD, Aaton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Google Scholar 

  • Praag HM van (1982) Depression. Lancet II:1259–1264

    Google Scholar 

  • Soubrié P (1987) Reconciling the role of central serotonin neurons in human and animal behaviour. Behav Brain Sci (in press)

  • Spyraki C, Fibiger HC (1981) Behavioural evidence for supersensitivity of postsynaptic dopamine receptors in the mesolimbic system after chronic administration of desipramine. Eur J Pharmacol 74:195–206

    Google Scholar 

  • Taylor DP, Riblet LA, Stanton HC, Eison AS, Eison MS, Temple DL Jr (1982) Dopamine and antianxiety activity. Pharmacol Biochem Behav 17 [Suppl 1]:25–35

    Google Scholar 

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

    Google Scholar 

  • Tricklebank MD, Forler C, Fozard JR (1984) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino) tetralin in the rat. Eur J Pharmacol 106:271–282

    Google Scholar 

  • Tricklebank MD, Middlemiss DN, Neill J (1986) Pharmacological analysis of the behavioural and thermoregulatory effects of the putative 5-HT1 receptor agonist, RU-24969, in the rat. Neuropharmacology 25:877–886

    Google Scholar 

  • Tye NC, Iversen SD, Green AR (1979) The effects of benzodiazepines and serotonergic manipulations on punished responding. Neuropharmacology 18:689–695

    Google Scholar 

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Authors and Affiliations

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

    Mirjana Carli, Roberto Invernizzi, Luigi Cervo & Rosario Samanin

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  1. Mirjana Carli
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  2. Roberto Invernizzi
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  3. Luigi Cervo
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  4. Rosario Samanin
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Carli, M., Invernizzi, R., Cervo, L. et al. Neurochemical and behavioural studies with RU-24969 in the rat. Psychopharmacology 94, 359–364 (1988). https://doi.org/10.1007/BF00174690

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  • DOI: https://doi.org/10.1007/BF00174690

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