RESUMO
The open field test (OFT) is a basic and most widely used test for investigation in animal studies of the neurobiological basis of anxiety and screening for novel drug targets. Here, we present the results of an OFT for weakly electric fish Gnathonemus petersii. This study aimed to describe the behavioral response of G. petersii exposed to an OFT, simultaneously with an evaluation of electrical organ discharges (EOD), to determine whether any association between EOD and patterns of motor behavior in the OFT exists. Treatment of OFT activity and its temporal patterning was assessed for the whole 6-min trial as well as per-minute distributions of activity using a near-infrared camera and an EOD data acquisition system. Our results demonstrated that the time spent, distance moved, and time of activity were significantly higher in the periphery of the OFT arena. The zone preference pattern over the 6-min test session showed that G. petersii prefer the outer zone (83.61%) over the center of the arena (16.39%). The motor behavior of fish measured as distance moved, active time, and swim speed were correlated with the number of EODs; however, no relationship was found between EOD and acceleration.
RESUMO
Neuroactive steroid 20-oxo-5ß-pregnan-3α-yl L-glutamyl 1-ester (PA-Glu), a synthetic analogue of naturally occurring 20-oxo-5ß-pregnan-3α-yl sulfate (pregnanolone sulfate, PA-S), inhibits N-methyl-D-aspartate (NMDA) receptors and possesses neuroprotective properties and minimal adverse effects. Herein, we report in vivo effects of new structural modifications of the PA-S molecule: a nonpolar modification of the steroid D-ring (5ß-androstan-3α-yl L-glutamyl 1-ester, AND-Glu), attachment of a positively charged group to C3 (20-oxo-5ß-pregnan-3α-yl L-argininate dihydrochloride salt, PA-Arg) and their combination (5ß-androstan-3α-yl L-argininate dihydrochloride salt, AND-Arg). The first aim of this study was to determine the structure-activity relationship for neuroprotective effects in a model of excitotoxic hippocampal damage in rats, based on its behavioral correlate in Carousel maze. The second aim was to explore side effects of neuroprotective steroids on motor functions, anxiety (elevated plus maze) and locomotor activity (open field) and the effect of their high doses in mice. The neuroprotective properties of PA-Glu and AND-Glu were proven, with the effect of the latter appearing to be more pronounced. In contrast, neuroprotective efficacy failed when positively charged molecules (PA-Arg, AND-Arg) were used. AND-Glu and PA-Glu at the neuroprotective dose (1 mg/kg) did not unfavorably influence motor functions of intact mice. Moreover, anxiolytic effects of AND-Glu and PA-Glu were ascertained. These findings corroborate the value of research of steroidal inhibitors of NMDA receptors as potential neuroprotectants with slight anxiolytic effect and devoid of behavioral adverse effects. Taken together, the results suggest the benefit of the nonpolar D-ring modification, but not of the attachment of a positively charged group to C3.
