[Heterodimeric D1-D2 dopamine receptors: a review].

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.

[Neuromediator systems in the mechanisms of remission and recurrence in alcoholism].

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 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].

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.

[The biological mechanisms of a congenital predisposition to alcoholism].

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].

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 neurochemical mechanisms underlying possible recurrences of alcoholism].

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.

[The properties of the brain dopamine and GABA receptors in rats with chronic alcoholic intoxication with different ethanol withdrawal times].

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.

[Effects of morphine on adenylate cyclase activity in lymphocytes of healthy subjects and patients with alcoholism and opiate addiction].

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.

[The action of low doses of bromocryptin in experimental morphine abstinence in rats].

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.

[Participation of monoamines in the recuperative responses of the central nervous system following experimental injury to the anterior portions of the cerebral cortex].

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.

[Effect of apomorphine on rat brain opiate receptors].

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.

[Effect of blockers of serotonin and noradrenaline synthesis on learning with emotionally different reinforcement in rats].

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.

[Characteristics of rat training on emotionally varied reinforcement under conditions of an oriented change in the level of brain serotonin and noradrenaline].

The effect of serotonin and noadrenaline precursors on the training of the animals on emotionally different reinforcement was studied. 5-OTP (10 mg/kg) facilitated the training of rats on the food reinforcement, but aggravated it on the pain reinforcement. D, L-DOPA (20 mg/kg) facilitated the training on the food reinforcement.

[Study of the dynamics of hepataene and pentaene formation by a culture of Streptoverticillium mucoheptinicum strain 44B/1 in the process of biosynthesis].

In the process of growth Streptoverticillium mycoheptinicum, strain 44B/I produced simultaneously a two-component pentaenic antibiotic (mycopenten) and a heptaenic antibiotic (mycoheptin) by the 1st day of cultivation. The ratio of the components remained constant during the whole fermentation process. When grown on the medium with sodium thiosulfate (under conditions of the changed medium potential) the culture produced the heptaen and a mixture of the components with the background absorption of the UV spectrum at 290--360 nm.

Effect of a unilateral cortical lesion on the monoamine content in the cat brain.

The serotonin and noradrenalin content in the cerebral cortex, hypothalamus, and mesencephalon was investigated spectrofluorometrically in 12 cats on the 5th-6th day after the production of a pathological focus in the region of the occipital cortex. Diffuse changes of brain activity were recorded on the EEG at this period: spike-like waves and slow waves of increased amplitude. A considerable increase in the serotonin concentration was observed in the cortex, with the effect predominant in the region immediately adjacent to the pathological focus.

[Changes in the cerebral serotonin and noradrenaline levels in the brains of white rats trained with emotionally different reinforcement].

The changes in the serotonin (5-OT) and noradrenaline (NA) content in the brain of rats taught on the emotionally-positive (food) and emotionally-negative (pain) reinforcement were compared. The process of animal learning was accompanied by increase in the biogenic amine level. But when the teaching was conducted on the emotionally-positive reinforcement there was a greater increase in the 5-OT and NA level than in the case of the emotionally negative reinforcement.