Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness

Title:Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness

Volume: 15 Issue: 3

Author(s): Francesca Demontis, Francesca Serra and Gino Serra

Affiliation:

Keywords: Animal models, bipolar disorder, depression, mania, memantine, mood stabilizer.

Abstract: Background: Mania seems to be associated with an increased dopamine (DA) transmission. Antidepressant treatments can induce mania in humans and potentiated DA transmission in animals, by sensitizing DA D2 receptors in the mesolimbic system. We have suggested that the sensitization of D2 receptors may be responsible of antidepressant-induced mania. This review aims to report the experimental evidence that led to the hypothesis that antidepressant-induced DA receptors dysregulation can be considered an animal model of bipolar disorder.

Methods: We reviewed papers reporting preclinical and clinical studies on the role of DA in the mechanism of action of antidepressant treatments and in the patho-physiology of mood disorders.

Results: A number of preclinical and clinical evidence suggests that mania could be associated with an increased DA activity, while a reduced function of this neurotransmission might underlie depression. Chronic treatment with imipramine induces a sensitization of DA D2 receptors in the mesolimbic system, followed, after drug discontinuation, by a reduced sensitivity associated with an increased immobility time in forced swimming test of depression (FST). Blockade of glutamate NMDA receptors by memantine administration prevents the imipramine effect on DA receptors sensitivity and on the FST.

Conclusion: We suggest that chronic treatment with antidepressants induces a behavioural syndrome that mimics mania (the sensitization of DA receptors), followed by depression (desensitization of DA receptors and increased immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover the observation that memantine prevents the “bipolar-like” behavior, suggests that the drug may have an antimanic and mood stabilizing effect. Preliminary clinical observations support this hypothesis.

Cite this article as:

Demontis Francesca, Serra Francesca and Serra Gino, Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness, Current Neuropharmacology 2017; 15 (3) . https://dx.doi.org/10.2174/1570159X14666160715165648

DOI https://dx.doi.org/10.2174/1570159X14666160715165648	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190