Neurochemical mechanisms of the defensive behavior in the dorsal midbrain.

Some regions in the mesencephalon, such as dorsal periaqueductal gray, inferior colliculus and deep layers of superior colliculus have been grouped together as a continuous strip of midbrain structures involved in the integration of the different components of aversive states in the brain. In fact, escape behavior and defensive, or fear-like behavior often result when these sites are electrically or chemically stimulated. Moreover, the behavioral responses induced by stimulation of these structures are, in general, accompanied by increases in mean arterial blood pressure, heart rate and respiration, and by analgesia. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum was shown to be attenuated by minor tranquilizers, probably through enhancement of GABAergic neurotransmission. Besides GABAergic interneurons which exert a tonic inhibitory control on neural circuits responsible for the behavioral correlates of the aversion in the above-mentioned structures, several other mechanisms such as opioid, neuropeptides, serotonergic and excitatory amino acids have also been implicated in the regulation of these processes. As to the analgesia that accompanies these aversive states it is mediated by non-opioid mechanisms, particularly by serotonergic ones through 5-HT2 receptors. Now, efforts have been made to characterize the mode of action of these neurotransmitters on their multiple receptors and how they interact with each other to produce or regulate the neural substrates of aversion in the midbrain.

Ethopharmacological analysis of behaviour of rats using variations of the elevated plus-maze.

Besides allowing better observation and recording of the behaviour of rodents, we have shown that the elevated plus-maze with transparent walls is as sensitive to anxiolytic and anxiogenic drug effects as a traditional apparatus with opaque walls. In this study we extend these observations with an ethopharmacological analysis of the behaviour of rats in the elevated plus-maze with transparent walls. A factor analysis of the behaviour of control (saline-treated) rats on the modified maze and on a standard maze revealed a characteristic distribution of the behavioural categories in six factors. For the modified maze, the first three factors, representing standard indices of anxiety, locomotion and risk assessment, were similar to the factor distribution reported by this and other studies using the standard elevated plus-maze test. Distinct features appeared on Factor 4, with the loading of rears in the modified maze together with the occurrence of the percentage of centre time and flat-back approach common to both mazes. Scanning and grooming, which are generally grouped on Factor 5 in the standard maze, appeared as isolated behavioural elements loading on Factors 5 and 6, respectively, in the modified maze. An ethopharmacological analysis of behaviour in the modified maze showed that midazolam (1 and 2 mg/kg) produced an anxioselective profile, whereas pentylenetetrazol (5 and 10 mg/kg) produced an anxiogenic-like profile. These results point to the distinct features of the elevated plus-maze with transparent walls, which may be beneficial in the study of the different facets of anxiety and the mode of action of anxiolytic drugs in rats.

Behavioral and pharmacological validation of the elevated plus maze constructed with transparent walls.

In this study we compared the performance of male Wistar rats, weighing 250-300 g, submitted to the standard plus maze (vertical surfaces of the closed arms with opaque walls) to their performance in a modified maze with raised Plexiglas edges in the closed arms (transparent walls). The animals (N = 12 for each group) continued to show a clear preference for the closed arms with transparent walls of the modified elevated plus maze. In addition, exploratory activity was higher in the open arms of the modified plus maze (4.25 +/- 0.42 entries and 53.50 +/- 5.10 s) as compared to that of the standard plus maze (2.10 +/- 0.25 entries and 24.00 +/- 4.91 s). Intraperitoneal injection of midazolam produced an increase in the number of entries (6.40 +/- 1.21 and 8.50 +/- 1.15 for 1.0 and 2.0 mg/kg, respectively) and in the time spend in the open arms (85.32 +/- 14.56 and 125.50 +/- 22.16 s for 1.0 and 2.0 mg/kg, respectively) while pentylenetetrazole caused a decrease in the number of entries (3.68 +/- 0.54 and 2.33 +/- 0.62 for 5.0 and 10 mg/kg, respectively) and in the time spent in the open arms of the modified maze (39.60 +/- 6.67 and 23.60 +/- 6.40 s for 5.0 and 10 mg/kg, respectively). The anxiolytic effect of midazolam and the anxiogenic effect of pentylenetetrazole were similar to those usually reported in the literature by authors using the standard test. These results behaviorally and pharmacologically validate the elevated plus maze with transparent walls and suggest that this test could be a useful tool for the study of anxiolytic drugs and the neurobiology of anxiety.

Behavioral and pharmacological validation of the elevated plus maze contructed with transparent walls

In this study we compared the performance of male Wistar rats, weighing 250-300g, submitted to the standard plus maze (vertical surfaces of the closed arms with opaque walls) to their performance in a modified maze with raised Plexiglas edges in the closed arms (transparent walls). The animals (N = 12 for each group) continued to show a clear preference for the closed arms with transparent walls of the modified elevated plus maze. In addition, exploratory activity was higher in the open arms of the modified plus maze (4.25 ñ 0.42 entries and 53.50 ñ 5.10s) as compared to that of the standard plus maze (2.10 ñ 0.25 entries and 24.00 ñ 4.91 s). Intraperitoneal injection of midazolam produced an increase in the number of entries (6.40 ñ 1.21 and 8.50 ñ 1.15 for 1.0 and 2.0 mg/Kg, rspectively) and in the time spent in the open arms (85.32 ñ 14.56 and 125.50 ñ 22.16 s for 1.0 and 2.0 mg/Kg, respectively) while pentylenetetrazole caused a decrease in the number of entries (3.68 ñ 0.54 and 2.33 ñ 0.62 for 5.0 and 10 mg/Kg, respectively) and in the time spent in the open arms of the modified maze (39.60 ñ 6.67 and 23.60 ñ 6.40 s for 5.0 and 10 mg/Kg, respectively). The anxiolytic effect of midazolam and the anxiogenic effect of pentylenetetrazole were similar to those usually reported in the literature by authors using the standard test. The4se results behaviorally and pharmacologically validate the elevated plus maze with transparebnt walls and suggest that this test could be a useful tool for the study of anxiolytic drugs and the neurobiology of anxiety