[Show abstract][Hide abstract] ABSTRACT: Zinc is an essential element which has considerable interaction with gamma-aminobutyric acid A type receptors (GABA(A)) and glutamate receptors in the cen tral nervous system (CNS). It is believed that zinc acts as a potent inhibitor of glutamate N-methyl-D-aspartate (NMDA) receptors, and binding to structurally specific site on the GABA(A) receptor leads to inhibition of GABA-dependent Cl-pass. The aim of our research was to test the anxiolytic and antidepressant effects of zinc after single application and its influence on general behavioural parameters after repeated administration.
Male Wistar rats were treated with increasing doses of zinc histidine dehydrate (10, 20, 30 mg/kg, i.p.). To determine anxiolytic and antidepressant properties of zinc two models were used: elevated plus maze (EPM) and forced swim test (FST). Behavioural parameters (stillness and mobility) were, also, recorded after single and repeated administration of active substance.
Testing animals in the EPM showed a statistically significant difference as follows: dose of 20 mg/kg significantly increased the time animals spent in open arms, indicating an acute anxio lytic effect, while doses of 30 mg/kg significantly reduced the time in the open arms, indicating a potentially anxiogenic ef fect. Testing the animals by FST showed a statistically signifi cant difference in immobility time of animals treated with the lowest applied (10 mg/kg) and highest applied (30 mg/kg) doses of zinc, compared to the control group. The first day of testing behavioral parameters showed the tendency to in crease locomotor activity of the animals with the lowest dose of zinc (10 mg/kg), while the following day revealed a reduced activity with the highest dose applied (30 mg/kg).
Zinc has important effects on the CNS: After single application, in all doses zinc showed antidepressant ef fects. The effects of zinc on anxiety and locomotor activity showed dose-dependent bidirectional effects.
[Show abstract][Hide abstract] ABSTRACT: There are several modulatory sites at GABA(A) receptors, which mediate the actions of many drugs, among them benzodiazepine. Three kinds of allosteric modulators act through the benzodiazepine binding site: positive (agonist), neutral (antagonist), and negative (inverse agonist). The goal of the present study was to examine the influence of the inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) acting on α GABA(A) receptor and compare its dose-response effects on memory and depression-like behavior. We independently studied the effects of DMCM (0.05-1.0mg/kg) on retention versus acquisition of active avoidance and depression-like behavior in the forced swim test. Throughout the study, drugs were given intraperitoneally, 30min before testing. ANOVA has showed that treatment with DMCM significantly affected retrieval of avoidance response (p<0.05), exerted promnesic effects in inverted U-shape manner. Dunnett's test indicated that the DMCM avoidance-facilitatory dose was 0.1mg/kg. At the dose facilitating retrieval of avoidance memory, DMCM significantly (p<0.05, comparison of regression coefficients by Student's t-test) and progressively increased acquisition rate during 5 days training, compared to the saline group. In forced swim test, ANOVA indicated statistically significant effects of DMCM (p<0.05). Dunnett's analysis showed that DMCM significantly decreased immobility time at the dose of 0.1mg/kg, exerted acute antidepressant-like effects. Our results experimentally support the findings that under certain circumstances, nonselective benzodiazepine site inverse agonists, produce memory-enhancing and antidepressant-like effects. The molecular and neuronal substrates linking the actions of specific GABA-benzodiazepine receptor complex subunits remains to be further elucidated.
Behavioural brain research 08/2012; 235(2):195-9. DOI:10.1016/j.bbr.2012.07.032 · 3.03 Impact Factor