[Heterodimeric D1-D2 dopamine receptors: a review]. / Geteromernye kompleksy D1-D2-dofaminovykh retseptorov: obzor literaturnykh dannykh.

This review summarizes modern data on the structure and functions ofheteromersformed by D1 and D2 dopamine receptors focusing on their role in the mechanisms of drug dependence. This article discusses potential functional significance of heterodimeric D1-D2 dopamine receptorsdue to their localization in the brain as well as unique pharmacological propertiesversus constituent monomers. It is shown that heteromerization results in dramatic changes in activated signaling pathways compare to the corresponding monomers. These studies update our current knowledge of ligand-receptor interactions and provide better understanding of dopamine receptors pharmacology. Furthermore elucidation of significance of heterodimeric D1-D2 dopamine receptors as drug targets is important for the development of new effective drug addiction treatment.

[Neuromediator systems in the mechanisms of remission and recurrence in alcoholism]. / Neiromediatornye sistemy v mekhanizmakh remissii i retsidiva pri alkogolizme.

Experiments on chronically alcoholic rats have revealed profound changes in the properties of the brain dopamine, serotonin, GABA and opiate systems 48 hours and 2 months of alcohol deprivation. With this, a single administration of ethanol showed its increased sensitivity of striatal and hippocampal receptors both during short- and long-term alcohol deprivation, the properties of these receptors tended towards recovery. It may be suggested that the above changes in the receptor apparatus of the neurotransmitter systems underlie the mechanism of remission and recurrence in alcoholism.

Some biological mechanisms of the inborn predisposition to alcoholism.

The children of alcoholism patients have a high biological risk of this illness, mental and emotional disorders, and behavioral disturbances. The offspring of white mongrel rats with chronic alcohol intoxication were investigated in order to study the neurochemical mechanisms of these phenomena. The content of DA in blood and blood plasma, the characteristics of GABA and the opiate receptors of the brain, the activity of DBH, COMT, MAO, the content of cAMP and cGMP in brain tissue, as well as the expression of the gene c-fos were studied. Changes in the brain content of DA and qualitative and quantitative changes in MAO (an increase and solubilization of MAO A and B activity in the liver) were identified in the offspring of alcoholic rats. A tendency was also observed in the brain toward a decrease in the activity of DBH and COMT and an increase in the activity of cAMP and cGMP. The baseline expression of the gene c-fos in the offspring of male alcoholic rats did not differ from the norm; however, a powerful increase in the expression of the gene c-fos did appear in response to the administration of 2 g/kg of ethanol, in the absence of this effect in the control. A view is presented on the significant role of changes in the functions of the DA system in the genesis of pathology in the offspring of parents with chronic alcohol intoxication, as well as on the possible influence of the prolonged consumption of alcohol on the function of the genome.

[Changes in the properties of the brain opiate, DA2, GABA, and 5-HT1 receptors in the progeny of female rats consuming ethanol for a long time during pregnancy and lactation]. / Izmenenie svoistv opiatnykh, DA2-, GAMK- i 5HT1-retseptorov mozga u potomkov krys-samok, dlitel'no potrebliavshikh étanol vo vremia beremennosti i laktatsii.

The study was undertaken to examine two-week and two-month rats whose mothers had been given alcohol for a long period of time during pregnancy and lactation. Profound changes were found in the properties of all types of the receptors under study. The changes were found in the receptors of both group animals. Substantial changes were encountered in the properties of GABA and DA2 receptors in the brain of two-month rats after acute alcoholization. The changes were differentiated from those seen in GABA and DA2 receptors in the brain of the rats whose mothers had not been given ethanol.

[The biological mechanisms of a congenital predisposition to alcoholism]. / Nekotorye biologicheskie mekhanizmy vrozhdennoi predraspolozhennosti k alkogolizmu.

In descendants of white rats with chronic alcoholic intoxication, the contents of DA in the brain and blood plasma, characteristics of GABA and opiate brain receptors, the contents of cAMP and other substances were studied as well as the c-fos gene expression. The data obtained suggest a considerable role of the changes in the DA system functions in the genesis of pathology in these descendants.

[Changes in the properties of the 5-HT1 receptors in the brains of rats, the progeny of parents consuming morphine for a long time]. / Izmenenie svoistv 5-HT1-retseptorov mozga u krys--potomkov roditelei, dlitel'no potrebliavshikh morfin.

Studies were performed in two-month rats whose parents had been given morphine for a long period before mating. Considerable changes were found in the properties of rat brain 5-HT1 receptors, which manifested as increased number of ligand binding sites (Bmax) and higher KD, which indicates a lower receptor affinity for ligand. Single morphine administration to the animals caused normalization of the properties of the receptors.

[The properties of the brain dopamine and GABA receptors in rats with chronic alcoholic intoxication with different ethanol withdrawal times]. / Svoistva dofaminovykh i GAMK-retseptorov mozga u krys s khronicheskoi alkogol'noi intoksikatsiei pri razlichnykh srokakh lisheniia étanola.

Marked changes in dopamine and GABA receptors in the brain of rats with chronic alcohol intoxication were registered 48 h and 3 months after ethanol withdrawal. The changes in dopamine receptors characterized by the increased number of the sites of binding with ligand (Bmax) were most pronounced 48 h after ethanol withdrawal. In 3 months the properties of these receptors tended toward recovery. The changes in GABA receptors also manifested by the increase in Bmax become further pronounced 3 months after ethanol withdrawal.

[The neurochemical mechanisms underlying possible recurrences of alcoholism]. / Izuchenie nekotorykh nerokhimicheskikh mekhanizmov, lezhashchikh v osnove vozmozhnykh retsidivov alkogolizma.

Experiments on chronic alcoholized rats revealed the similar changes in brain dopamine receptors, in brain and blood catecholamines as well as in blood cyclic adenosine monophosphate during both short- and long-term alcohol deprivation. It is concluded that such changes may form material basis for alcoholism relapses.

[Effects of morphine on adenylate cyclase activity in lymphocytes of healthy subjects and patients with alcoholism and opiate addiction]. / Vliianie morfina na aktivnost' adenilattsiklazy limfotsitov zdorovykh, bol'nykh alkogolizmom i opiinoi narkomaniei.

The morphine dose 10(-7) M had practically no effect on adenylate cyclase (AC) activity in lymphocytes of healthy controls (n = 20). The same dose of morphine had a pronounced stimulating effect on the AC activity in lymphocytes of alcoholics in withdrawal (n = 16). In the group of opiate addicts in withdrawal (n = 9) morphine had also a stimulating effect, which differed significantly from controls (33.7 +/- 13.8; P. 0.02). The range of fluctuation of morphine influence on AC activity during the first week of hospitalization was 162.9 +/- 33.0% in alcoholics and 30.4 +/- 4.6% in opiate addicts (P 0.01).

[The action of low doses of bromocryptin in experimental morphine abstinence in rats]. / Deistvie malykh doz bromokriptina pri éksperimental'noi morfinnoi abstinentsii u krys.

In experiments on rats which consumed for a long time morphine solution as a drinking liquid there was studied the effect of low doses of bromocriptine on the behavioural manifestations of morphine abstinence syndrome and the condition of the noradrenergic, dopaminergic and conjugated GABAergic systems of the brain. It was shown that the preliminary administration of bromocriptine decreased the degree of the withdrawal syndrome that correlated with the restoration of dopamine content and the normalization of the condition of D2-dopaminergic receptors in different regions of the brain. Bromocriptine exerted no influence on the morphine withdrawal-induced changes in the condition of GABA receptors of the cerebral cortex.

Morphine influence on adenylate cyclase activity in peripheral blood lymphocytes of alcoholic patients.

The effect of morphine on adenylate cyclase activity in lymphocytes was tested in 20 normal controls, 16 alcoholics in withdrawal and 9 sober alcoholics. Alcoholics in withdrawal were characterized by a significantly increased stimulatory effect of morphine, whereas sober alcoholics showed an inhibitory effect. The morphine effect was abolished by naloxone and correlated with the severity of withdrawal and alcohol intoxication.

[Effect of apomorphine on rat brain opiate receptors]. / Vliianie apomorfina na opiatnye retseptory golovnogo mozga krys.

Stereospecific binding of apomorphine to rat brain opiate receptors was shown by assaying the competition of 7,8(n)--3H--naloxone and D-ala2-tyrosyl-3,5-3H--enkephalin (5-D-leucine) for opiate receptor binding. EC-NaCl50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone and D-ala2, D-leu5-enkephalin in the absence of NaCl were 20 and 42 microM, respectively. EC+NaCl 50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone in the presence of 100 mM NaCl was 17 microM. From the ratio of EC+NaCl 50 to EC-NaCl the value of "sodium shift" of effective concentration can be calculated as 0.85. From the data obtained it is concluded that apomorphine, like naloxone, is a "pure" antagonist but it has much less affinity for enkephalin and opiate binding sites. The probable mechanisms of the pharmacological action of apomorphine are discussed.

[Participation of monoamines in the recuperative responses of the central nervous system following experimental injury to the anterior portions of the cerebral cortex]. / Uchastie monoaminov v vosstanovitel'nykh reaktsiiakh tsentral'noi nervnoi sistemy pri éksperimental'nom povrezhdenii perednikh otdelov kory golovnogo mozga.

The role of biogenic amines (serotonine and noradrenalin) in the compensatory recovery processes was studied by means of conditioned reflexes in chronic experiments on rats after extirpation of the forebrain cortex. The recovery reactions are shown to proceed in the presence of significant shifts in the level of biogenic amines. Injection of 5-hydroxytryptophan to the operated on animals promotes rapid recovery of disturbed conditioned reflexes. It is suggested tht the increased serotonin brain level raises its compensatory potencies.

[Effect of blockers of serotonin and noradrenaline synthesis on learning with emotionally different reinforcement in rats]. / Vliianie blokatorov sinteza serotonina i noradrenalina na obuchenie krys pri émotsional'no razlichnom podkreplenii.

The effect of inhibitor of serotonin and norepinephrine synthesis in the brain on learning was investigated in rats with emotionally different reinforcement. Parachlorphenylalanine (320 mg/kg) was shown to inhibit learning with food reinforcement, but facilitated learning with pain reinforcement. Disulfiram (100 mg/kg) inhibited learning with pain reinforcement considerably, but failed to influence learning with food reinforcement. Alpha-methyl-m-thyrosine inhibited both forms of learning. These new facts are in line with our previous data on mediating role of the brain monoaminergic systems between emotions and memory.