Vol 13, No 2 (2015)

The purpose of the paper was to study both the desacylghrelin (unacylated ghrelin) level in the blood serum and expression of mRNA ghrelin receptor in the brain structures in ontogeny after chronic alcoholization in rats. The results proved that the prenatal effect of ethanol negatively affected the maturation of dopaminergic and ghrelin systems of the brain as well as involvement of ghrelin system in mechanisms of alcohol dependence formation. The decrease of COMT mRNA expression simultaneoully with the increase of expression of D2 long and short isoforms of dopaminergic receptors and misbalance of ghrelin system were observed. Alcoholization of mothers reduced desacylghrelin level in the blood serum in early postnatal period in offsprings although mRNA expression of ghrelin receptor in the brain was elevated. Chronic alcoholization of adult rats also affected the ghrelin system. In the alcoholiztion process, the reduced contents of desacylghrelin in the blood serum with compensatory increase of ghrelin receptor expression in the brain were registered. After withdrawal of ethanol, the recovery of desacylghrelin level (tendency to normalization) was observed.

The orexin family of hypothalamic neuropeptides has been implicated in reinforcement mechanisms relevant to both food and drug reward. Previous behavioral studies with antagonists at the orexin A-selective receptor OX(1), have demonstrated its involvement in behavioral sensitization, conditioned place-preference, self-administration and reinstatement of drugs abuse. There are dense concentrations of hypocretin receptors, in brain regions implicated in drug reinforcement processes, such as the nucleus accumbens, ventral tegmental area and bed nucleus of the stria terminalis Adult male Wistar rats were implanted the stimulating electrodes to the lateral hypothalamus. Simultaneously, the microcanules were implanted into the BNST to inject the OX(1) receptor antagonist. Rats were trained to perform intracranial self-stimulation. The effects of the OX(1)-selective antagonist SB-408124 on brain stimulation-reward (BSR) were measured. SB-408124 injected into the BNST (1µg/1 µl in volume for each injection.) alone had no effect on self-stimulation of lateral hypothalamus. Amphetamine (1 mg/kg i.p.) potentiated BSR, measured as lowering of BSR threshold and enhancing of BSR frequency. Amphetamine-induced stimulatory effects on intracranial self-stimulation was blocked by injections of SB-408124 into BNST. These data demonstrate that OX(1) play an important role in regulating the reinforcing and reward-enhancing properties of amphetamine and suggest that orexin transmission is likely essential for establishing and maintaining the amphetamine habit in human addicts. However, the observations that OX1 antagonism reduce brain reward and block stress- and cue-induced reinstatement of drug-seeking suggests that this class of compounds may be useful additions to stress-reduction and other behavioral therapies in the treatment of substance abuse disorders.

The oxidative and immune status was assessed in a rat model of inflammatory and degenerative damages of the smooth parodont tissue due to administration of 2 % formaldehyde water solution (0.3 ml) into the smooth parodont tissues. The lipid peroxidation indexes (malonic dialdehyde and dienic conjugates level) were 3.6-5.8-fold higher in the blood serum and parodont tissue in 3 days after inflammation beginning. The inflammation was accompanied by inhibition of lymphokin-producing function of lymphocytes in reaction of inhibition of leucocytes migration with concanavalin A (Con A) by 39 % and with phytohaemagglutinin (PGA) by 37 %. The activity of oxygen-independent microbicide system of phagocytes was decreased by 13 %, that was typical for subacute duration of inflammatory process. The phagocyte number was increased by 26 % and the phagocytosis index by 22 % with decrease of phagocytes participating in phagocytosis by 31 %. The spontaneous NBT-test index was increased by 63 %, and stimulating one by 35 %. Trekrezan administered for 3 days decreased malonic dialdehyde level by 61 %, dienic conjugates level by 68 %, in 2.9-fold increased the concentration of recovered glutatione and superoxide dismutase activity by 79 %. Simultaneously, the elevation of lymphokin-producing function of lymphocytes in reaction of inhibition of leucocytes migration with Con A by 67 % and with PGA by 73 % was registered. Phagocyte activity of neutrophils was increased by 24 %. Phagocyte number equal to middle number of microorganisms phaged by one active neutrophil and phagocytosis index were decreased by 26 % and 14 % respectively. Trekrezan administered orally revealed the same but less significant action. Preliminary administration of lidocaine intragastrally for blockade of gastric afferents did not affect the trekrezan action. Therefore, trekrezan possesses both anti-inflammatory and immune stimulating action. Oral administration of trekrezan induced more weak effect than after intraperitoneal administration and did not depend on activation of gastric afferents.

Obtusifole and umbelliferone had low toxicity after enteral administration. Even high obtusifole doses demonstrated weak anticonvulsant activity in the models of maximal electroshock (MES) and pentamethylentetrasole seizures (LD 100). These coumarines were not effective in the models of strychnine- and thiosemycarboside-induced convulsions. They revealed neurotoxical influence, reducing unconditioned reflex, normal adoptive mice behavior and did not prevent the loss of conditioned passive avoiding reflex (CPAR) after MES. These coumarines did not antagonize with synthetic anticonvulsants. The Haplophyllum obtusifolium grass decoction administered enterally was not toxic, because LD minimal might not be fixed. It had no neurotoxical properties, prevented the loss of CPAR and mortality after MES, elevated tolerance to convulsive-mortal pentamethylentetrasole and strychnine action. So this decoction demonstrated cerebroprotective properties. The use of Haplophyllum obtusifolium in traditional medicines of Asiatic states may not be explained by only coumarines. It is based on cerebroprotective properties of this medicine.