Our behavioral studies have shown that MK-801 (an NMDA receptor antagonist) causes deficits in social behavior in rodents, reducing both the number of episodes and duration of social interaction. Risperidone (an atypical antipsychotic) at high dose (0.1 mg / kg, i.p.) blocked these behavioral deficits. Administration of inactive doses of risperidone in conjunction with an antidepressant (mirtazapine, escitalopram) also inhibited MK-801-induced behavioral deficiency.
Both risperidone alone (0.1 mg / kg) and the combined administration of an inactive dose of risperidone with mirtazapine or escitalopram counteracted MK-801-induced memory impairments in mice. These results suggest that co-administration of a low dose of risperidone with an antidepressant (e.g. escitalopram or mirtazapine) may be beneficial in the treatment of some dysfunctions associated with chronic schizophrenia, especially negative symptoms and cognitive impairments. Behavioral and biochemical assays for evaluation of antidepressant-like activity showed that the combination of risperidone and low doses of antidepressants has synergistic effects. Moreover, it was found that this positive interaction involves serotonin 5-HT1A receptors and adrenergic α2 receptors, as well as brain-derived neurotrophic factor (BDNF) and interleukins (particularly interleukin 10). These results suggest that co-administration of risperidone and low doses of antidepressants could be potentially useful in the treatment of drug-resistant depression.
Additionally, our team is involved in ongoing research evaluating the role of sigma receptor ligands in central nervous system disorders. The subject of the research is the mechanism of action and potential therapeutic properties of sigma1 receptor agonists (including PB190, a novel sigma1 receptor ligand). We have demonstrated that sigma1 receptor agonists (PB190 and DTG) co-administered with fluvoxamine (SSRI antidepressant) exerts an antidepressant-like effect in the swimming test and the tail suspension test, as well as anxiolytic activity evaluated in appropriate animal models.
Behavioral tests to assess antipsychotic effects (social interaction test in rats, novel object recognition test in mice and rats).
Behavioral tests to assess antidepressant effects (swimming test in mice and rats, tail suspension test, spontaneous locomotor activity in mice and rats).
Behavioral tests to assess anxiolytic effects in rats (elevated plus maze) and mice (four-plate test)
Behavioral tests to assess cognitive impairments (passive avoidance test)
The most important discoveries in the last 3 years
It has been demonstrated that antidepressants (escitalopram, mirtazapine) potentiated the effects of low doses of risperidone (an atypical antipsychotic) in animal models.
It has been shown that the combination of risperidone and a low dose of antidepressants has synergistic effects and this positive interaction involves serotonin 5-HT1A receptors and adrenergic α2 receptors, as well as brain-derived neurotrophic factor (BDNF) and interleukins (particularly interleukin 10).