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Antidepressant effects of pramipexole, a novel dopamine receptor agonist

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Summary

Pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochloride), a new dopamine receptor agonist with preference for D3 compared to D2 and D4 receptors, was tested in rats in respect of its potential antidepressant activity. In the forced swimming test the drug under study, given three times in rats, reduced the immobility time. In the forced swimming test, joint treatment with antidepressants (imipramine, amitriptyline) and pramipexole evoked a more potent effect than any of the drugs given alone; however, the locomotor hyperactivity was weaker after joint administration. Citalopram and fluoxetine, inactive per se in the forced swimming tests, visibly enhanced the antidepressant-like effect of pramipexole but, on the other hand, they attenuated the locomotor hyper-activity evoked by the drug. Repeated treatment with pramipexole (0.3 or 1 mg/kg, twice daily for 14 days) increased the locomotor activity measured at 1h after the last dose. Repeated administration of pramipexole (as above) potentiated the D-amphetamine- or quinpirole-induced locomotor hyperactivity.

The obtained results indicate that, in the tests used, pramipexole evokes effects similar to those of typical antidepressants and, at the same time, enhances their activity (the forced swimming test in rats); therefore it may be regarded as a potential antidepressant drug.

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References

  • Borsini F (1995) Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev 19: 377–395

    PubMed  Google Scholar 

  • Camacho-Ochoa M, Walker EL, Evans DL, Piercey MF (1995) Rat brain binding sites for pramipexole, a clinically useful D3-prefering dopamine agonist. Neurosci Lett 196: 97–100

    PubMed  Google Scholar 

  • Carter AJ, Müller RE (1991) Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo. Eur J Pharmacol 200: 65–72

    Google Scholar 

  • Cervo L, Grignaschi G, Rossi C, Samanin R (1991) Role of central serotonergic neurons in the effect of sertraline in rats in the forced swimming test. Eur J Pharmacol 196: 217–222

    PubMed  Google Scholar 

  • Górka Z, Wojtasik E, Kwiatek H, Maj J (1979) Action of serotoninmimetics in the behavioral despair test in rats. Comm Psychopharmacol 3: 133–136

    Google Scholar 

  • Klimek V, Maj J (1989) Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors. J Pharm Pharmacol 41: 555–558

    PubMed  Google Scholar 

  • Levant B, Grigoriadis DE, DeSouza EB (1993) [3H]Quinpirole binding to putative D2 and D3 dopamine receptors in rat brain and pituitary gland: a quantitative autoradiography study. J Pharmacol Exp Ther 264: 991–1001

    PubMed  Google Scholar 

  • Maj J (1984) Mechanism of action of antidepressant drugs given repeatedly: changes in the responses mediated by noradrenaline (α1) and dopamine receptors. In: Paton W, Michell J, Turner P (eds) IUPHAR 9th International Congress of Pharmacology, London, 1984. Proceedings, vol 3. Macmillan, London, pp 137–143

    Google Scholar 

  • Maj J (1986) Repeated treatment with antidepressant drugs: responses mediated by brain dopamine receptors. In: Hippius H, Klerman GL, Matussek N (eds) New results in depression research. Springer, Berlin Heidelberg New York Tokyo, pp 90–98

    Google Scholar 

  • Maj J, Rogóż Z, Skuza G (1982) Fluvoxamine — a new antidepressant drug fails to show antiserotonin activity. Eur J Pharmacol 81: 287–292

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Maj J, Rogóż Z, Skuza G, Sowińska H (1985) The effect of repeated treatment with antidepressant drugs on the action of D-amphetamine and apomorphine in rats. In: Kelemen K, Magyar K, Vizi ES (eds) Neuropharmacology '85. Akademiái Kiadó, Budapest, pp 133–139

    Google Scholar 

  • Maj J, Rogóż Z, Skuza G, Sowińska H (1989) Antidepressants given repeatedly increase the behavioural effect of dopamine D-2 agonist. J Neural Transm 78: 1–8

    Google Scholar 

  • Maj J, Dziedzicka-Wasylewska M, Rogóż R, Rogóż Z, Skuza G (1996) Antidepressant drugs given repeatedly change the binding of the dopamine D2 receptor agonist, [3H]N-0437, to dopamine D2 receptors in the rat brain. Eur J Pharmacol 304: 49–54

    PubMed  Google Scholar 

  • Maj J, Rogóż Z, Skuza G, Kołodziejczyk K (1997) The behavioural effects of pramipexole, a novel dopamine receptor agonist on the dopamine system. Eur J Pharmacol (submitted)

  • Malinge M, Bourin M, Colombel MC, Larousse C (1988) Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test. Psychopharmacology 96: 104–109

    PubMed  Google Scholar 

  • Mierau J, Schingnitz G (1992) Biochemical and pharmacological studies on pramipexole, a potent and selective dopamine D2 receptor agonist. Eur J Pharmacol 215: 161–170

    PubMed  Google Scholar 

  • Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajines ME, Huff RM (1995) Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol, Mol Pharmacol Sect 290: 29–36

    Google Scholar 

  • Nixon MK, Hascoet M, Bourin M, Colombel MC (1994) Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system. Psychopharmacology 115: 59–64

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Sautel F, Griffon N, Lévesque D, Pilon C, Schwartz J-C, Sokoloff P (1995) A functional test identifies dopamine agonists selective for D3 versus D2 receptors. NeuroReport 6: 329–332

    PubMed  Google Scholar 

  • Schneider CS, Mierau J (1987) Dopamine autoreceptor agonists: resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine. J Med Chem 30: 494–488

    PubMed  Google Scholar 

  • Serra G, Argiolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25: 415–424

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Svensson K, Carlsson A, Huff RM, Kling-Petersen T, Waters N (1994) Behavioral and biochemical effects of the D3 preferring agonist R-(+)-7-OH-DPAT and pramipexole suggest functional differences between dopamine D2 and D3 receptors. Eur J Pharmacol 263: 235–243

    PubMed  Google Scholar 

  • Willner P, Lappas S, Cheeta S, Muscat R (1994) Reversal of stress-induced anhedonia by the dopamine receptor agonist, pramipexole. Psychopharmacology 115: 454–462

    PubMed  Google Scholar 

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Maj, J., Rogóż, Z., Skuza, G. et al. Antidepressant effects of pramipexole, a novel dopamine receptor agonist. J. Neural Transmission 104, 525–533 (1997). https://doi.org/10.1007/BF01277669

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  • DOI: https://doi.org/10.1007/BF01277669

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