[Increase in the level of orexin receptor 1 (OX1R) mRNA in the brain structures of rats prone to impulsivity in behavior]. / Povyshenie urovnia mRNK retseptora oreksina pervogo tipa (OX1R) v strukturakh golovnogo mozga u krys, sklonnykh k impul'sivnosti v povedenii.

Orexin and its receptors are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this work was to study the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The expression of the OX1R gene was higher in the hypothalamus by 122% and in the hippocampus by 149% in rats that preferred to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. In the prefrontal cortex, on the contrary, no significant changes were observed in the level of OX1R mRNA. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data indicate involvement of OX1R in the hypothalamus and hippocampus in mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.

Effects of Fluorencarbonic Acid Derivative on the Levels of Monoamines and Their Metabolites in Brain Structures of Rats with Modeled Depression-Like State.

The effects of the new structural analogue of benactyzine, a derivative of fluorencarbonic acid, on monoamine levels in brain structures were studied in male Wistar rats with experimental depression. Depressive state in rats was modeled by single injection of reserpine (4 mg/kg). The concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus and striatum were measured by HPLC. It was found that preliminary treatment (30 days) with the derivative of fluorencarbonic acid prevented a decrease in monoamine level in the hypothalamus (NE, 5-HT, and 5-HIAA) and striatum (DA, 5-HT, and 5-HIAA). The neurochemical shifts (correction of 5-HT deficiency and stabilization of DA and NE levels) correlated with the high antidepressant activity of this agent observed in Porsolt forced swimming test.

[Participation of GABA- and dopaminergic mechanisms of the bed nucleus of stria terminalis in reinforcing effects of psychotropic drugs mediated via the lateral hypothalamus].

The purpose of the investigation was to elucidate significance of GABA and dopamine systems of the bed nucleus of stria terminalis for the reinforcing effects of a number of psychotropic drugs (opiates, opioids, psychostimulants) on self-stimulation of the lateral hypothalamus in rats. To the Wistar male rats, bipolar electrodes were implanted in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcannules were implanted into the bed nucleus of stria terminalis to inject the drugs under study. Some drugs, xycaine, or lidocain, a blocker of sodium influx ionic currents, antagonists of GABAA receptors bicuculline, D1 dopamine receptors SCH23390 and D2 dopamine receptors sulpiride which were administered intrastructurally into the bed nucleus of stria terminalis, were used for pharmacological analysis. Xycaine > SCH23390 = bicuculline inhibited self-stimulation of the lateral hypothalamus. The reinforcing properties of a number of psychoactive drugs (amphetamine, Fentanyl, sodium ethaminal and leuenkephaline) were changed on the background of their action. It is concluded that the bed nucleus of stria terminalis controls the hypothalamic self-stimulation via GABA- and dopaminergic mechanisms. GABA realizes the negative (inhibitory) action. The direct positive (activating) effect on the lateral hypothalamus is realized through D1 dopamine receptors, and D2 dopamine receptors of the bed nucleus of stria terminalis limit the positive effects of narcogenic drugs.

[Significance of CRF and dopamine receptors in amygdala for reinforcing effects of opiates and opioids on self-stimulation of lateral hypothalamus in rats].

Bipolar electrodes were implanted in the lateral hypothalamus in a group of 44 Wistar male rats in order to study self-stimulation reaction in the Skinner box. Simultaneously, microcanules were implanted into the central nucleus of the amygdala to inject the drugs (1 microl per injection). The blockade of corticoliberin (CRF) receptors (astressin, 1 microg) or Na+influx currents (xycaine or lidocain 1 microg) by the intrastructural administration of drugs into the amygdala decreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D1 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg) respectively, also reduced self-stimulation but to a lower degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) retained their psychoactivating effect on self-stimulation (+30-37%), while fentanyl (0.1 mg/kg) and leu-enkephaline (0.1 mg/kg) did not produce this effect. Fentanyl moderately activated self-stimulation only after the blockade of D1 dopamine receptors with SCH23390. After the blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating action of amygdala on the hypothalamus is eliminated, the enhancing effects of opiates (fentanyl) and opioids (leu-encephaline) are blocked, but the effects of psychomotor stimulant amphetamine and barbiturate sodium ethaminal are retained.

[The extended amygdala system and self-stimulation of the lateral hypothalamus in rats: modulation with opiates and opioids].

Wistar male rats were implanted with bipolar electrodes in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcanules were implanted into the central nucleus of the amygdala to inject the drugs studied (1 microl in volume for each injection). The blockade of CRF receptors (astressin 1 microg) or sodium influx ionic currents (xycaine, or lidocain 1 microg) by means of intrastructural administration of drugs into the amygdala descreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D2 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg), respectively. reduced self-stimulation too, but in less degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors, as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) supported their psychoactivating effect on self-stimulation (+30-37%), but fentanyl (0.1 mg/kg) had got no effect. Fentanyl activated self-stimulation moderately only after blockade D1 dopamine receptors with SCH23390. After blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating influence of the amygdala on the hypothalamus is diminished, the reinforcing effects of opiated (fentanyl) and opioids (leuencephaline) will block, but there will be no effect for psychomotor stimulant amphetamine and barbiturate sodium ethaminal.

[Chronicles of St. Petersburg pharmacology (on 210th anniversary of the Department of Pharmacology of the St. Petersburg State Military Medical Academy)].

The Department of Pharmacology of the St. Petersburg Military Medical Academy (until 1881, the Medical-Surgery Academy) was founded in 1798 among the first seven departments of the Academy, being referred to as the Chair of "Materia Medica" in terms of that time and having the present name since 1808. Generations of outstanding Russian pharmacologists used to work here, including A. P. Nelyubin, O. V. Zabelin, I. P. Pavlov, S. V. Anichkov, M. P. Nikolaeva, V. V. Zakusov, N. V. Lazarev, and V. M. Vinogradov. At present, the Department of Pharmacology successfully continues the search for new drugs producing antihypoxic, antioxidant, actoprotector, and nootropic action, develops basic concepts in the understanding of factors inducing drug dependence, and studies synaptic and hormonal mechanisms of reinforcement regulation.

[Expression of mRNA for corticoliberin and vasopressin in hypothalamus and amygdala on the background of administration of psychoactive drugs in rats].

Wistar male rats were injected intraperitoneally for 4 days in elevated doses with: (1) physiological saline (control; 0.1 - 0.2 - 0.4 - 0.8 ml/rat), (2) amphetamine (0.5 - 1.0 - 2.0 - 4.0 mg/kg); (3) fentanyl (0.00625 - 0.0125 - 0.025 - 0.05 mg/kg), (4) 40% aqueous ethanol solution (0.5 - 1.0 - 2.0 - 4.0 g/kg), (5) ethaminal sodium (2.5 - 5 - 10 - 20 mg/kg), and (6) dexamethasone (0.5 - 1.0 - 2.0 - 4.0 mg/kg). The forced regime of drug administration led to gradual load of the organism and prevented drug tolerance development. This method is widely used for the formation of drug dependence (or its features) due to various narcotic agents. The maximum level of mRNA expression for corticoliberin was registered in amygdala after the administration of dexamethasone (0.46 units compared to beta-actin), and the minimum level was observed after treatment with sodium ethaminal (0.07) and fentanyl (0.037). In hypothalamus, sodium ethaminal produced elevated mRNA expression (0.8 units), followed by ethanol (0.37) and fentanyl (0.039). Amphetamine activated mRNA expression for corticoliberin neither in hypothalamus nor in amygdala for all of the drugs studied. The mRNA expression for vasopressin was also not registered for all drugs in hypothalamus and amygdala. Therefore, the reinforcing system of hypothalamus supports the typical reaction on the administration of narcotic agents, while the extended amygdala system includes both the proper reinforcement and the stress reactivity elements.

Expression of mRNA for corticotropin-releasing hormone and vasopressin in the hypothalamus and amygdala of rats after administration of narcogenic.

Male Wistar rats received intraperitoneal injections of physiological saline (control), phenamine, fentanyl, ethanol, sodium ethaminal, or dexamethasone in increasing concentrations for 4 days. Forced administration of these drugs provided gradual load of the organism and prevented the development of tolerance. Such approach is extensively used for the development of drug addiction or several manifestations of this state. Expression of corticotropin-releasing hormone mRNA in the amygdala was maximum after administration of dexamethasone (0.46 arb. units vs. beta-actin), but was much lower in experiments with sodium ethaminal and fentanyl (0.07 and 0.037 arb. units, respectively). In the hypothalamus, enhanced mRNA expression was observed after injection of sodium ethaminal, ethanol, and fentanyl (0.8, 0.37, and 0.039 arb. units, respectively). Phenamine did not increase mRNA expression in the amygdala and hypothalamus. Expression of vasopressin mRNA was not detectable in brain structures of animals from various groups. Our results indicate that the hypothalamic reinforcement system provides a similar response to narcogens, whereas the extended amygdala includes elements of both reinforcement and stress reactivity.

Comparison of behavioral effects of cortexin and cerebrolysin injected into brain ventricles.

We compared central effects of polypeptide preparations cortexin and cerebrolysin injected into brain ventricles of Wistar rats in doses of 1, 10, and 100 microg. Both drugs exhibited moderate psychoactivating effect, the effects cortexin were more pronounced compared to those of cerebrolysin in all tests.

Comparison of the effects of dopamine agonists on self-stimulation of the hypothalamus with lesioning of mesolimbic brain structures in rats reared in conditions of social isolation.

Initial and phenamine-stimulated frequencies of self-stimulation of the lateral hypothalamus were not significantly different in rats reared in communities and in conditions of social isolation. Unilateral lesioning of the ventral tegmental area and the medial prefrontal cortex in early ontogenesis increased phenamine sensitivity only in isolated rats. The dopamine receptor agonist apomorphine, at a dose of 0.05 mg/kg, which affects presynaptic receptors, inhibited the self-stimulation response in intact group-reared animals and in rats reared in isolation, by 21-23%. Stimulation of the ventral tegmental area did not change, while stimulation of the medial prefrontal cortex doubled the sensitivity of rats to apomorphine in animals reared in isolation (at doses of 0.05 and 0.5 mg/kg). Conditions of partial sensory and complete species isolation resulted in the development of a state of presynaptic receptor hypersensitivity of dopamine receptors in mesocorticolimbic brain systems in rats.

[Mnemonic effects of substituted amides of imidazole-4(5)-carboxylic acid in rats]. / Izuchenie mnesticheskikh éffektov zameshchennykh amidov imidazol-4(5)-karbonovoi kisloty u krys.

The effects of four derivatives of imidazole-4(5)-carboxylic acid on the formation and extinction of the conditioned drinking reflex and the preservation of the conditioned response of passive avoidance after electroconvulsive shock or mechanic craniocerebral injury were studied during experiments on rats. N-methylamide of imidazole-4(5)-carboxylic acid exhibited the greatest psychostimulant and antiamnestic activity. Addition of beta-phenylisopropyl radical to NH2-group resulted in the appearance of depressant properties.

[Treatment of experimental destruction of the duodenum with preparations with nootropic action]. / Lechenie éksperimental'nykh destruktsii dvenadtsatiperstnoi kishki preparatami nootropnogo deistviia.

In the experiments on rats the peptic ulcer of duodenum was simulated by means of mechanic compression of reflexogenic zones of pylorus and intestine. The destruction of duodenal mucosa was developed in 3-4 hours after the compression and retained in the course of 5-6 days. Piracetam (200 mg/kg) and etimizol (3 mg/kg) eliminated and cimetidine (25 mg/kg), solcoseryl (0.5 mg/kg) and metacine (5 mg/kg) diminished the destruction after the course of 6 injections of each drug with an interval of 10-12 hours. Therapeutic effects of piracetam and etimizol correlated with their ability to return towards normal concentration of creatine phosphate.

[Effect of the intracisternal administration of the neurotoxins 6-hydroxydopamine and 5,7-dihydroxytryptamine on the formation of the passive avoidance reaction and the biogenic amine level in the brain of rats]. / Vliianie vnutritsisternal'nogo vvedeniia neirotoksinov 6-oksidofamina i 5,7-dioksitriptamina na formirovanie reaktsii passivnogo izbeganiia i uroven' biogennykh aminov v mozge krys.

In Wistar rats, intracisternal administration of 6-hydroxydopamine caused a 3.0-3.5-fold decrease in noradrenaline and dopamine levels whereas 5,7-dihydroxytryptamine led to a 2.5-fold reduction of the serotonin content in the hypothalamus. The degeneration of serotoninergic neurons produced by 5,7-dihydroxytryptamine did not affect passive avoidance response while the lesion of catecholaminergic neurons with 6-hydroxydopamine disturbed it. Participation of the brain monoaminergic system in the mechanisms of conditioning is discussed.

[Antiamnestic properties of pyrazole dicarboxylic acid derivatives in rats]. / Izuchenie antiamnesticheskikh svoistv proizvodnykh pirazoldikarbonovoi kisloty u krys.

Eight derivatives of pyrazole dicarboxylic acid (IEM-565, IEM-476, IEM-1332, IEM-474, IEM-373, IEM-440, IEM-1333, IEM-439) have been studied in rats for the ability to abolish the amnesia of passive avoidance behavior induced by electroconvulsive shock IEM-476, IEM-373 and IEM-439 have proved to be the most efficacious.