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Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats.
Behav Pharmacol. 2010 Feb; 21(1):21-8.BP

Abstract

Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors.

Authors+Show Affiliations

Dipartimento di Scienze del Farmaco, Università di Sassari bPharmacovigilance - Medical Department, Gentium SpA, Villa Guardia (CO), Italy. dsfpaolo@uniss.itNo 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

20009921

Citation

D'Aquila, Paolo S., et al. "Dopamine Is Involved in the Antidepressant-like Effect of Allopregnanolone in the Forced Swimming Test in Female Rats." Behavioural Pharmacology, vol. 21, no. 1, 2010, pp. 21-8.
D'Aquila PS, Canu S, Sardella M, et al. Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats. Behav Pharmacol. 2010;21(1):21-8.
D'Aquila, P. S., Canu, S., Sardella, M., Spanu, C., Serra, G., & Franconi, F. (2010). Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats. Behavioural Pharmacology, 21(1), 21-8. https://doi.org/10.1097/FBP.0b013e32833470a7
D'Aquila PS, et al. Dopamine Is Involved in the Antidepressant-like Effect of Allopregnanolone in the Forced Swimming Test in Female Rats. Behav Pharmacol. 2010;21(1):21-8. PubMed PMID: 20009921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats. AU - D'Aquila,Paolo S, AU - Canu,Silvia, AU - Sardella,Marco, AU - Spanu,Caterina, AU - Serra,Gino, AU - Franconi,Flavia, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/13/medline SP - 21 EP - 8 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 21 IS - 1 N2 - Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/20009921/Dopamine_is_involved_in_the_antidepressant_like_effect_of_allopregnanolone_in_the_forced_swimming_test_in_female_rats_ L2 - http://dx.doi.org/10.1097/FBP.0b013e32833470a7 DB - PRIME DP - Unbound Medicine ER -