Chronic cocaine injections attenuate behavioral response of kappa-opioid receptors to U-50,488H agonist.

Chronic injections of cocaine (20 mg/kg daily for 10 days) increase activity and decrease anxiety in male C57Bl/6j mice in comparison with animals chronically injected with normal saline. U-50,488H (kappa-opioid receptor agonist; 2.5 mg/kg) produced an anxiolytic effect in animals preinjected with normal saline and had no effect in animals chronically injected with cocaine. Presumably, chronic activation of dopaminergic systems caused by cocaine injections is paralleled by desensitization of kappa-opioid receptor system.

[Dynamic changes of brain serotonergic and dopaminergic activities during development of anxious depression: experimental study]. / Dinamicheskue izmeneniia serotonergicheskoi i dofaminergicheskoi aktivnosti mozga v protsesse razvitiia trevozhnoi depressii: éksperimental'noe issledovanie.

Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-HT1A-receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.

[Changes in the expression of monoaminergic genes under the influence of repeated experience of agonistic interactions: from behavior to gene]. / Izmeneie ékspressii monoaminergicheskikh genov pod vliianiem povtornogo opyta agonisticheskikh vzaimodeistvii: ot povedeniia k genu.

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.

[Modifying effect of the repeated experience of agonistic confrontations on effect of naltrexone in male mice]. / Modifitsiruiushchee vliianie povtornogo opyta agonisticheskikh vzaimodeistvii na éffekty naltreksona u samtsov myshei.

In mice with different experience of agonistic confrontations: victories or social defeats during 3 and 10 days (T3 and T10 winners and T3 and T10 losers, resp.), T10 winners displayed a lesser aggression and a more hostile behaviour than T3 winners. Naltrexone dose-dependently decreased attacks in the T3 winners and did not affect aggressive grooming, diggings, autogrooming, and exploratory activity. Naltrexone was ineffective in T10 winners. The naltrexone effects were similar in T3 and T10 losers and its high and low doses contrarily affected different parameters of submissive behaviour. The repeated experience of agonistic confrontations seems to modify the naltrexone effects depending on a neurochemical background, differing in winners and losers.

[Effect of long-term restraint stress on behavior of female C57BL/6J and CBA/Lac inbred mice. Dispersion and cluster analysis]. / Vliianie dlitel'nogo restriktsionnogo stressa na povedenie samok myshei inbrednykh linii C57BL/6J i CBA/Lac. Dispersionnyi i klasternyi analizy.

An augmented exploratory behaviour and motor activity and diminished anxiety after a restraint stress were found in CBA/Lac female mice [corrected] but not in C57BL/6J ones. In the Porsolt test the result was exactly opposite. A possibility of inherent anxiety-depressive pathological condition in the C57BL/6J mice [corrected] developing under the effect of repeated psychological stress, is assumed.

Behavioral effect of 1A-serotonin receptor agonist ipsapirone in mice previously defeated in male-male encounters.

The effect of 1A-serotonin receptor agonist ipsapirone (3 mg/kg) on mouse behavior was studied in the "wall" and Porsolt tests. The effects of the test drug were compared in intact animals and mice previously defeated in 20 intermale encounters (victims). Ipsapirone was ineffective in victims and effective in intact mice in the wall test. In the Porsolt test the drug prolonged stupor in victims.

[The characteristics of the functional activity of the brain serotoninergic system in the manifestation of natural and pathological anxiety in mice: the effect of the genotype]. / Osobennosti funktsional'noi aktivnosti serotoninergicheskoi sistemy mozga v proiavlenii estestvennoi i patologicheskoi trevozhnosti u myshei: vliianie genotipa.

Anxiety was estimated in intact male mice of C57BL/6J (C57) and (CBA) and CBA/Lac (CBA) strains and in males of both strains after the repeated experience of social defeats (losers) in 10 daily aggressive confrontations. A plus-maze test for behavior in a novel situation and a partition test for communicative activity were applied. Tryptophan hydroxylase (TPH) activity, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the midbrain, hypothalamus, amygdala, hippocampus, and striatum in losers and controls (5 days of individual housing of intact animals). Intact C57 mice which demonstrated active avoidance in the maze had reduced TPH activity in the all studied brain regions compared to the intact CBA mice with passive behavior. The 5-HT catabolism in intact C57 was lower in the midbrain and hypothalamus and higher in amygdala, hippocampus, and striatum than in CBA mice. Chronic social stress led to expressed anxiety revealed by both tests in C57 losers in contrast to CBA ones. This anxiety was accompanied by an increase in 5-HIAA level and 5-HIAA/5-HT ratio in the midbrain as well as by an increase in 5-HT level and decrease in 5-HIAA level and 5-HIAA/5-HT ratio in the hippocampus of C57 losers in comparison with the controls. Flesinoxan (0.5 mg/kg, i.p.), 5-HT1A receptor agonist, changed the communicative behavior of controls but was ineffective in losers. Thus, a decrease in sensitivity of 5-HT1A receptors was suggested in stress-induced anxiety of C57 losers. The less expressed anxiety in CBA losers was associated with less expressed changes in serotonergic metabolism. It is concluded that serotonergic mechanisms of pathological anxiety induced by the long-term social stress and those of natural anxiety in intact mice are different.

[The behavior of mice from 6 genotypes in 2 tests for anxiety]. / Povedenie myshei shesti genotipov v dvukh testakh na trevozhnost'.

Mice from six inbred strains (CBA, ICR, SWR, BALB/c, DBA/2, and C57BL/6J) were tested for anxiety in elevated plus-maze and light-dark box. In the elevated plus-maze CBA, ICR, and SWR mice spent more time in the open area (open arms and the center of the maze) than BALB/c and, especially, DBA/2 and C57BL/6J mice. A significant negative correlation was revealed between the percent of time spent in the open area and the number of peepings from the enclosed arms. There was no correlation between the percent of the open-area time and the number of entries into the open arms. A positive correlation was found between the percent of the open-area time in the plus-maze test and percent of time spent in the white section of the light-dark box. Mice of SWR strain spent 64 percent of the experimental time in the white section, whereas C57BL/6J mice spent in the illuminated section of the box only 15 percent of time. A significant interaction was found between the main index of anxiety (percent of the open-area time in the box) and indices of exploratory activity (number of crossed squares and number of rearings) in the light-dark test.

[The participation of the brain dopamine D1 and D2 receptors in the process of the development of depression induced by social confrontations in mice]. / Uchastie D1 i D2 dofaminovykh retseptorov mozga v protsesse razvitiia depressii, indutsirovannoi sotsial'nymi konfrontatsiiami u myshei.

Brain D1 and D2 receptors were studied in male mice with repeated experience of social defeats in daily intermale aggressive confrontations inducing development of experimental depression. Groups of animals were studied after 10 (T10 losers) and 20 (T20 losers) days of agonistic confrontations. Mice after 5 days of individual housing were used as a control group. In the experimental groups D1/D2 antagonist cisfluphentixol (0.2 mg/kg) did not affect the communicative behavior in the partition test that estimated behavioral reactivity of a male to another one. Selective D2 antagonist sulpiride (20 mg/kg), however, decreased these reactions in the control group and, in particular, in T10 losers but was ineffective in T20 losers. Both antagonists changed behavior in Porsolt's test of the control mice and, to a greater extent, of T10 losers but failed to change it in T20 losers. Decrease in Bmax in nucleus accumbens and increase in Kd in amygdala were revealed in T20 losers with [3H]-SCH 23390 binding assay. The obtained evidence shows that development of DISC is accompanied by D1 and D2 receptor sensitivity changes. Analysis of data suggests the specific participation of D1 receptors of the mesolimbic dopaminergic system at the stage of developed DISC.