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Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies.
Pol J Pharmacol. 2004 Mar-Apr; 56(2):179-85.PJ

Abstract

Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptor, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either of drugs given alone. Since it has been suggested that, in addition to their other functions, dopamine and alpha(1)-adrenergic receptors may play a role in behavioral response in the forced swimming test, in the present study we examined the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in combination with IMI in the forced swimming test in rats. We also measured the level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA (20 mg/kg) produced stronger antidepressant-like effect than either of agents given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the forced swimming test) inhibited an antidepressant-like effect induced by co-administration of IMI and AMA. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and AMA failed to enhance the locomotor activity of rats, measured in the open field test. Also sulpiride and prazosin did not decrease the exploratory activity induced by co-administration of IMI and AMA. The above result suggests that the dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism of synergistic action of IMI and AMA in the forced swimming test in rats. The pharmacokinetic interaction can be excluded, since AMA did not change significantly the antidepressant level in the rat plasma and brain, measured 1 h after exposure to the forced swimming test.

Authors+Show Affiliations

Department of Pharmacology, Institute of Pharmacology, Polsih Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.plNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15156068

Citation

Rogóz, Zofia, et al. "Synergistic Effect of Imipramine and Amantadine in the Forced Swimming Test in Rats. Behavioral and Pharmacokinetic Studies." Polish Journal of Pharmacology, vol. 56, no. 2, 2004, pp. 179-85.
Rogóz Z, Skuza G, Kuśmider M, et al. Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies. Pol J Pharmacol. 2004;56(2):179-85.
Rogóz, Z., Skuza, G., Kuśmider, M., Wójcikowski, J., Kot, M., & Daniel, W. A. (2004). Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies. Polish Journal of Pharmacology, 56(2), 179-85.
Rogóz Z, et al. Synergistic Effect of Imipramine and Amantadine in the Forced Swimming Test in Rats. Behavioral and Pharmacokinetic Studies. Pol J Pharmacol. 2004 Mar-Apr;56(2):179-85. PubMed PMID: 15156068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies. AU - Rogóz,Zofia, AU - Skuza,Grazyna, AU - Kuśmider,Maciej, AU - Wójcikowski,Jacek, AU - Kot,Marta, AU - Daniel,Władysława A, PY - 2003/12/01/received PY - 2004/01/28/revised PY - 2004/5/25/pubmed PY - 2005/1/19/medline PY - 2004/5/25/entrez SP - 179 EP - 85 JF - Polish journal of pharmacology JO - Pol J Pharmacol VL - 56 IS - 2 N2 - Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptor, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either of drugs given alone. Since it has been suggested that, in addition to their other functions, dopamine and alpha(1)-adrenergic receptors may play a role in behavioral response in the forced swimming test, in the present study we examined the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in combination with IMI in the forced swimming test in rats. We also measured the level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA (20 mg/kg) produced stronger antidepressant-like effect than either of agents given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the forced swimming test) inhibited an antidepressant-like effect induced by co-administration of IMI and AMA. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and AMA failed to enhance the locomotor activity of rats, measured in the open field test. Also sulpiride and prazosin did not decrease the exploratory activity induced by co-administration of IMI and AMA. The above result suggests that the dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism of synergistic action of IMI and AMA in the forced swimming test in rats. The pharmacokinetic interaction can be excluded, since AMA did not change significantly the antidepressant level in the rat plasma and brain, measured 1 h after exposure to the forced swimming test. SN - 1230-6002 UR - https://www.unboundmedicine.com/medline/citation/15156068/Synergistic_effect_of_imipramine_and_amantadine_in_the_forced_swimming_test_in_rats__Behavioral_and_pharmacokinetic_studies_ L2 - http://www.if-pan.krakow.pl/pjp/pdf/2004/2_179.pdf DB - PRIME DP - Unbound Medicine ER -