Involvement of the monoaminergic system in the antidepressant-like activity of chromium chloride in the forced swim test.

Bio-metal chromium(III) is a crucial microelement for the proper functioning of living organisms. Previous preclinical and clinical studies reported its potential antidepressant properties. The aim of the present study was to examine the effect of antidepressants and noradrenergic and dopaminergic receptor antagonists on chromium chloride (CrCl3) activity in the forced swim test (FST) in mice and rats. Imipramine (5 mg/kg), fluoxetine (5 mg/kg) and reboxetine (5 mg/kg) but not bupropion (1 mg/kg), administered jointly with CrCl3 at a dose of 6 mg/kg, reduced the immobility time in the FST in mice. The reduction of the immobility time induced by the active dose (12 mg/kg) of CrCl3 was completely abolished by propranolol (2 mg/kg, ß-adrenoceptor antagonist), SCH 23390 (0.5 mg/kg, a dopamine D1 receptor antagonist), and partially by prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist) and sulpiryd (50 mg/kg, a dopamine D2/D3 receptor antagonist) administration. The locomotor activity was significantly reduced by CrCl3 + reboxetine treatment, which did not influence the reboxetine enhancement of the antidepressant-like effect of CrCl3 in the FST. Moreover, CrCl3 at a dose of 32 mg/kg (although not at 12 mg/kg) significantly reduced the immobility and enhanced the climbing (but not swimming) time in the FST in rats, which indicates the involvement of the noradrenergic pathway in this effect. The present study indicates that the antidepressant-like activity of chromium in the FST is dependent (although to a different extent) on the noradrenergic, dopaminergic and serotonin systems.

The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test.

Antidepressant-like activity of zinc in the forced swim test (FST) was demonstrated previously. Enhancement of such activity by joint administration of zinc and antidepressants was also shown. However, mechanisms involved in this activity have not yet been established. The present study examined the involvement of the NMDA and AMPA receptors in zinc activity in the FST in mice and rats. Additionally, the influence of zinc on both glutamate and aspartate release in the rat brain was also determined. Zinc-induced antidepressant-like activity in the FST in both mice and rats was antagonized by N-methyl-D-aspartic acid (NMDA, 75 mg/kg, i.p.) administration. Moreover, low and ineffective doses of NMDA antagonists (CGP 37849, L-701,324, D-cycloserine, and MK-801) administered together with ineffective doses of zinc exhibit a significant reduction of immobility time in the FST. Additionally, we have demonstrated the reduction of immobility time by AMPA receptor potentiator, CX 614. The antidepressant-like activity of both CX 614 and zinc in the FST was abolished by NBQX (an antagonist of AMPA receptor, 10 mg/kg, i.p.), while the combined treatment of sub-effective doses of zinc and CX 614 significantly reduces the immobility time in the FST. The present study also demonstrated that zinc administration potentiated a veratridine-evoked glutamate and aspartate release in the rat's prefrontal cortex and hippocampus. The present study further suggests the antidepressant properties of zinc and indicates the involvement of the NMDA and AMPA glutamatergic receptors in this activity.

Modulation of antidepressant-like activity of magnesium by serotonergic system.

The influence of magnesium on the action of antidepressants drugs with different pharmacological profiles citalopram, reboxetine and tianeptine, was investigated in the forced swim test (FST) in mice. Magnesium (10 mg Mg/kg) given with reboxetine (2.5 mg/kg) did not change the behavior of animals in the FST. A synergistic effect was seen when magnesium (10 mg Mg/kg) was given jointly with citalopram (15 mg/kg) or tianeptine (20 mg/kg) in the FST, without accompanying changes in locomotor activity. Moreover, the antidepressant-like effect of magnesium (30 mg Mg/kg) was significantly reduced by pretreatment of mice with an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 200 mg/kg). Thus, the antidepressant-like action of magnesium in the FST seems to involve an interaction with serotonergic system.

Influence of adenosine receptor agonists and antagonists on amphetamine-induced stereotypy in rats.

The influence of adenosine receptor agonists and antagonists on amphetamine-induced stereotypy was examined in male Wistar rats. Adenosine A2 receptor agonists CGS 21680 (0.5-2 mg/kg ip) and a non-specific A2/A1 receptor agonist NECA (0.05-0.1 mg/kg ip) attenuated in a dose dependent manner amphetamine-induced stereotypy (2 mg/kg sc). CPA as specific agonist of adenosine A1 receptors counteracted this stereotypy, but only in a narrow range of doses (0.1-0.2 mg/kg ip). Adenosine A2A receptor antagonist, DMPX (3 and 6 mg/kg ip) potentiated stereotypy induced by either subthreshold dose of amphetamine 0.5 mg/kg or a high one 2 mg/kg. A non-selective adenosine receptor antagonist, caffeine (10 mg/kg ip) potentiated effect of low dose of amphetamine, but only in a dose of 20 mg/kg ip increased stereotypy induced by 2 mg/kg ip of amphetamine. A selective adenosine A1 receptor antagonist CPT (1 and 3 mg/kg ip) was ineffective in reversing amphetamine-induced stereotypy. These results confirm the existence of adenosine-dopamine interactions in the brain, and the suggestions that A2 adenosine receptor agonists may have antipsychotic properties.