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.
Similar content being viewed by others
References
Borsini F (1995) Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev 19: 377–395
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
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
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
Górka Z, Wojtasik E, Kwiatek H, Maj J (1979) Action of serotoninmimetics in the behavioral despair test in rats. Comm Psychopharmacol 3: 133–136
Klimek V, Maj J (1989) Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors. J Pharm Pharmacol 41: 555–558
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
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
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
Maj J, Rogóż Z, Skuza G (1982) Fluvoxamine — a new antidepressant drug fails to show antiserotonin activity. Eur J Pharmacol 81: 287–292
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Willner P, Lappas S, Cheeta S, Muscat R (1994) Reversal of stress-induced anhedonia by the dopamine receptor agonist, pramipexole. Psychopharmacology 115: 454–462
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01277669