Functional roles of the monoaminergic and aminoacidergic mechanisms of the dorsal pallidum in anxiety of different aversive origins.

Microinjections of serotonin and glutamic acid into the globus pallidus in conditions of free selection between a light and a dark chamber showed these substances to have antiaversive activity in rats in the "threatening situation" test but not in the "illuminated area" test. Local administration of dopamine and GABA into this basal ganglia formation had no effect on the mechanisms of voluntary movement but countered anxiety states in both behavioral models. These results provide evidence that the neurotransmitter systems of the dorsal pallidum have different degrees of involvement in the operative control of behavior when the modality of the aversive stimulus changes.

[Functional significance of monoamine- and aminoacidergic mechanisms of dorsal pallidum in anxiety of different aversive genesis].

Microinjections of serotonin and glutamine acid into the globus pallidus reveal antiaversive properties of these subsrances in the test with avoiding "threatening situation" but not "illuminated site" test under conditions of rats' free choice between light and dark sites. Dopamine and GABA injected locally into this formation of basal ganglia do not affect the mechanisms of voluntary movement, but counteract the conditions of anxiety in both models of behavior. The results testify to unequal involvement of neurotransmitter systems of the dorsal pallidum into operative regulation of behavior with changes of aversive stimulus modality.

Neurochemical mechanisms of the dorsal pallidum in the antiaversive effects of anxiolytics in various models of anxiety.

In conditions in which rats had a free choice between dark and light chambers, microinjections of glutamic acid, serotonin, and campiron into the globus pallidus showed that these agents have antiaversive properties in a threatening situation test but not in an illuminated area test. Dopamine, apomorphine, GABA, chlordiazepoxide, phenibut, and indoter injected locally into this formation of the basal ganglia had no effect on the mechanisms of voluntary movement but counteracted anxiety states in both behavioral models. These results provide evidence that the monoaminergic and aminoacidergic systems of the dorsal pallidum have different functional roles in the operative regulation of behavior for aversive stimuli of different modalities.

[Neurochemical features of the ventral pallidum in realization of the antiaversive effects of anxiolytics in different models of anxiety].

Preliminary intraperitoneal injections of some combinations of adreno- and dopaminomimetics, monoamines, and mediator amino acids (as well as of their agonists and antagonists) followed by microinjections of the same combinations into the ventral pallidum reveal differences in the functional significance of the neurochemical profile of this paleostriatum formation in realization of the anxiety states of different genesis, as manifested in the "illuminated site avoidance" and the "threatening situation" tests in rats. The pharmacological analysis based on the local injection of anxiosedative and anxioselective agents into the ventral paleostriatum showed that the antiaversive action of campirone is revealed under the conditions of dominating fear motivation, while that analogous action of chlordiazepoxide, phenibut and indoter is revealed under negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic (rather than by cathecholamine- and glutaminergic) aversive systems of the ventral pallidum.

Neurochemical characteristics of the ventromedial hypothalamus in mediating the antiaversive effects of anxiolytics in different models of anxiety.

In experiments on rats using an "illuminated area" avoidance test and a "threatening situation" avoidance test, preliminary i.p. administration and subsequent microinjection into the ventromedial hypothalamus of various combinations of monoamines, transmitter amino acids, and their agonists and antagonists demonstrated differences in the functional importance of the neurochemical profile of this limbic formation in mediating anxiety states of different origins.

[Monoaminergic and aminoacidergic mechanisms of the posterior hypothalamus in realization of the antiaversive effects of anxiosedative and anxioselective agents in various anxiety models].

Experiments using the "illuminated site" and "threatening situation" avoidance tests on rats after preliminary intraperitoneal injection of monoamines, mediator amino acids, and their agonists and antagonists, followed by microinjection of the same combinations into the posterior hypothalamus revealed functional ambiguity in the neurochemical profile of this limbic brain formation in realization of the anxiety states of various genesis. Pharmacological analysis was performed after preliminary injection of various anxiosedative and anxioselective agents into the posterior hypothalamus. It was found that the antiaversive action of chloridiazepoxide, fenibut, and indoter is manifested only under conditions of dominating fear motivation and is mediated by a GABAergic mechanism in the posterior hypothalamus.

[Neurochemical characteristics of the ventromedial hypothalamus and anti-aversive effects of anxiolytic agents in various anxiety models].

Neurochemical analysis using anxiosedative and anxioselective agents injected into the hypothalamus revealed that antiaversive action of camprione is only realised under conditions of domineering fear motivation whereas that of chlordiazepoxide, phenibut, indoter may also be realised under conditions of negative stressful zoo-social impacts mediated by serotonin.

[Monoamine, GABA, and glutamergic mechanisms of the anterior hypothalamus in anti-aversive effects of sedative and selective drugs in various models of anxiety].

The experiments using "illuminated site" and "threatening situation" avoidance tests on rats microinjected with GABA, glutamic acid, monoamines and their agonists and antagonists, as well as anxiosedative and anxioselective agents into the anterior hypothalamus revealed functional ambiguity in the neurochemical profile of this limbic brain formation in the anxiety states of various aversive genesis. Preliminary intraperitoneal injection of the monoamine and GABA antagonists, followed by the local administration of the antianxiety drugs studied, showed that the antiaversive action of chlordiazepoxide, fenibut, and indoter is manifested in both anxiety models via a GABAergic mechanism in the anterior hypothalamus. The anxiolytic effect of campiron is manifested only under negative-stressor zoosocial conditions and is mediated by the serotoninergic systems of this limbic brain formation.

The role of neurochemical mechanisms of ventromedial hypothalamus in various models of anxiety in rats.

Microinjections of glutamic acid, serotonin, and sulpiride in the ventromedial hypothalamus reduced anxiety in an illuminated platform avoidance task in rats, while dopamine, apomorphine, picrotoxin, and memantine increased it. Similar injections of phenylephrine and yohimbine reduced anxiety in threatening situation task only, while GABA reduced it in both tasks. It is suggested that various emotional and stress phenotypes are realized through functionally different neurochemical mechanisms of ventromedial hypothalamus.

[The neurochemical profile of the caudate nucleus in the anxiolytic action of benzodiazepine and nonbenzodiazepine tranquilizers on different models of anxiety].

In the experiments on rats in avoidance response to "eliminated area" and "threatening situation" it is found that the microinjection of monoamines and amino-acids of mediator action, adreno- and dophaminemimetics, their antagonists, and blocker of GABAA receptors picrotoxine into dorsal and ventral sections of caudate nucleus elucidates different functional value and neurochemical special features of examined neostriatum specimens in realization of anxiety states of different origin. Local injection of chlordiazepoxide, phenibutum, indoterum, campirone and campironine into aforementioned sections of the caudate nucleus reduces the state of anxiety in "eliminated area" and/or "threatening situation" response tests thus revealing the similarity with well-known effects of GABA and serotonin and substantial difference in the effects of catecholamines and glutamine acid. It is found that anti-anxious effect of benzodiazepine and nonbenzodiazepine anxiolytics can be mediated through participation of neuron matrices of dorsal and ventral sections of the caudate nucleus having functionally ambiguous neurochemical profile.

[Study of monoamino- and amino acidergic mechanisms of the rat caudate nucleus in antiaversive effects of tranquilizers in various anxiety models].

Administration of anxio-sedative drugs into the rat caudate nucleus revealed that antiaversive effects of chlordiazepide, phemibut, and indoter only occur under dominating fear motivation, whereas antiaversive effects of campirone and campironine occur under the influence of negative or stressful zoo-social actions and are realised via the GABA- and serotoninergic type of synaptic switching in the dorsal part of the caudate nucleus.

[The neurochemical profile of the septal nucleus accumbens in the anxiolytic action of tranquilizers on different models of anxiety].

In experiments on rats with tests for avoidance of an "illuminated area" and a "threatening situation", microinjection into the septal nucleus accumbens of monoamines and GABA, adreno- and dopaminomimetics, and their antagonists demonstrated a different neurochemical profile of this brain structure in anxiety states of different genesis. Local injections of chlordiazepoxide, pnenibut, indoter, campiron, and campironin into the nucleus weakened the alarm in the test for avoidance of an "illuminated area" and/or a "threatening situation", showing a similarity to the effects of GABA and serotonin but not to those of mesaton (phenylephrine hydrochloride) and dopamine. It is concluded that the antialarm effect of benzodiazepine and nonbenzodiazepine anxiolytics may be mediated by switching into action of neuron matrices of the accumbens nucleus with a different neurochemical profile responsible for the operative control of behavior in changed modality of the aversive stimulus.

[Neurochemical analysis of the amygdala basolateral nucleus of rats during anxiety tests].

Chlordiazepoxid, phenibut, indoter, campiron, campironin, when administered into the amygdala, improve the anxiety condition of rats in avoidance tests and resemble by their effects dophamine, GABA, or serotonin. Observed differences in the anxiolytic effects between anxiosedative and anxioselective agents seem to be due to an unequal contribution of the monoamin- and aminoacidotergic transmitters into the mechanisms of heteromodal aversive anxiety genesis in the basolateral area of the amygdalar complex.

[The neurochemical mechanisms of the central amygdaloid nucleus and the anxiolytic action of tranquilizers in different models of anxiety states].

Chemical stimulation of the central nucleus of the amygdalar complex was carried out in rats during performance of tests of avoidance of "lighted square" and "threatening situation". Microinjections of monoamines, GABA, glutamate, some of their receptor agonists and antagonists revealed neurochemical heterogeneity of the structure and functional ambiguity of neurotransmitter systems in genesis of anxiety of different aversive modes. Chlordiazepoxid, phenibut, indoter, campiron, campironin decrease anxiety in the tests of avoidance of "lighted square" and "threatening situation", their effects being similar to those of dopamine, GABA, or serotonin.

The role of dopaminergic mechanisms on the brain in various models of anxious states.

In tests of "illuminated area" and the "threatening situation" avoidance by rats, apomorphine and phenamine, administered intraperitoneally, attenuate the state of alarm. A similar effect is observed when sulpiride, a selective blocker of D2-receptors of dopamine, and of picrotoxin, a GABA antagonist, are administered. Sulpiride effectively counteracts the anxiolytic effects of all of the dopaminomimetics investigated and of picrotoxin.

[The functional role of monoaminergic and amino acid-ergic mechanisms of the locus coeruleus in anxiety from different aversive origins].

Dopamine and glutamine acid microinjection in the locus coeruleus of rats does not influence the alarm state in the test of "Threatening situation" avoidance, but weakens the state of alarm in the test of "illuminated site" avoidance. The local injection of GABA and noradrenaline mesatone effect imitators in this brain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. On the contrary, the chemical stimulation of locus coeruleus by serotonin influences the anxiolytic effect in two different experimentally modelled states of alarm.

[The neurochemical profile of the dorsal hippocampus and the antiaversive effects of anxiolytics in different models of anxiety in rats].

Chemical stimulation of the dorsal hippocampus by serotonin and GABA decreases anxiety in a test of avoidance of precarious situation but not of illuminated platform. Intrahippocampal injection of chlordiazepoxide induced similar effect. Microinjection of glutamic acid into the hippocampus increases and that of dopamine decreases anxiety in the test of avoidance of illuminated platform but not of precarious situation.

[The mechanisms of the anxiolytic action of 1-(2-pyrimidinyl)-piperazine derivatives, serotonin agonists].

1-(2-pyrimidinyl)-piperazine derivatives (ipsapirone and campirone) injected intraperitoneally or into dorsalis nucleus raphe and dorsalis hippocampus of rats revealed dose-dependent anxiolytic action in avoidance procedure and conflict situations. 5-HT locally injected into the nucleus raphe and hippocampus revealed a role of serotoninergic mechanisms of these brain formations in the studied anxiety conditions of different aversive genesis. It is concluded that anxiolytic effect dissociation revealed in different anxiety tests, are stipulated by serotonin and its agonists due to nucleus raphe and hippocampus chemical stimulation my suggest their different neurochemical contribution and nonserotoninergic component involved in the mechanism of 1-(2-pyrimidinyl)-piperazine derivative anxiolytic action.

[The role of monoamin- and acidergic mechanisms of the hippocampus in anxiety states of different origins and their participation in the antiaversive effects of anxiolytics].

The experiments on rats with tests of avoiding "lighting square" and "threatening situation" and with the chemical stimulation of dorsal and ventral hippocampus with dopamine, 5-HT, GABA and glutamine acid, showed different functional significance of these monoamines and acidergic transmitters agents in the states of anxiety of heteromodal aversive genesis. It seems that the variations in the action spectrum of anxiolytics under study are due to unequal degree of 5-HT and GABA-ergic transmitter mechanisms of dorsal and ventral hippocampus.

[The GABA-ergic component of the anxiolytic action of 1-(2-pyrimidinyl)-piperazine derivatives].

The 1-(2-pyrimidinyl)-piperazine derivatives campirone, campironine, levopironine) evoked hyperpolarizing responses of rat dorsal root ganglion neurons mediated by 5-hydroxytryptamine(1A) receptor activation and, like chlordiazepoxide, potentiated neuronal responses evoked by GABA-depolarizing receptor activation. The drugs studied in the lighted space and threatening situation avoidance tests showed an anxiolytic effect. Picrotoxin was found to be effective in inhibiting the anxiolytic effect of chlordiazepoxide, levopironine and campironine, but it failed to affect the antianxious action of campirone.