[Change in dopamine and serotonin receptor sensitivity following chronic chlorpromazine administration]. / Izmenenie chuvstvitel'nosti dofaminovykh i serotoninovykh retseptorov posle khronicheskogo vvedeniia khlorpromazina.

Stereotypy elicited by apomorphine, or hyperactivity syndrome (head twitches) induced by 1-tryptophane plus phenelzine was studied in rats during 20 days following chlorpromazine administration for 10 days (10 mg/kg daily). Significant intensification of behavioural effect of apomorphine and especially of 1-tryptophane was observed in neuroleptically pretreated rats. These results point to the development of hypersensitivity of dopamine and serotonin receptors to agonists following chlorpromazine pretreatment. It is suggested that increase in the sensitivity of dopamine and serotonin receptors is of importance for the development of hyperkinetic syndrome during neuroleptic treatment.

[Role of benzodiazepine receptors in regulating aggressive behavior]. / O roli benzodiazepinovykh retseptorov v reguliatsii agressivnogo povedeniia.

In experiments of male Wistar rats, it was established that a long-term apomorphine treatment caused changes in density of benzodiazepine receptors in forebrain structures opposite to those elicited by acute administration. The changes in benzodiazepine binding correlated with decrease of antiaggressive effect of diazepam and Ro 15-1788 after long-term apomorphine administration. The action of apomorphine on the benzodiazepine receptors was not direct, as apomorphine did not change the benzodiazepine agonist-antagonist interaction, and naloxone, opiate blocator, was a more powerful antagonist of antiaggressive action of diazepam than Ro 15-1788. The involvement of the two types of benzodiazepine receptors in the regulation of aggressive behavior is suggested, the first being apparently linked with GABA and opiate receptors and the other one--with the serotoninergic system. Ro 15-1788 was able to antagonize the effects of diazepam on the first but not on the second type of benzodiazepine receptors.

[Intracerebroventricular administration of cholecystokinin inhibits the dopamine- and serotoninergic systems of the brain]. / Intratserebroventrikuliarnoe vvedenie kholetsistokinina ugnetaet aktivnost' dofamin- i serotoninergicheskoi sistem mozga.

In male Wistar rats, intraventricular administration of cholecystokinin caused specific dose-dependent behavioral changes: low doses (0.1--0.25 U) depressed the exploratory activity whereas higher doses (0.5--8.0 U) caused head twitches, stereotyped gnawing and hyperreactivity. Cholecystokinin suppressing markedly dopamine and serotonin turnover in various brain structures, completely blocked the behavioral effects of amphetamine (2.5 mg/kg) and 5-hydroxytryptophan (150 mg/kg). The data obtained suggest that cholecystokinin suppresses presynaptic dopamine- and serotoninergic mechanisms but enhances the sensitivity of postsynaptic receptors of these systems.

[Effect of multiple daily administration of fenibut and diazepam on GABA and benzodiazepine receptors in the mouse brain]. / Vliianie mnogodnevnogo vvedeniia fenibuta i diazepama na retseptory GAMK i benzodiazepinov v mozge myshei.

It was shown in experiments on mice that 25 hours after chronic treatment with fenibut (100 mg/kg, twice daily for 10 days) was discontinued the number of benzodiazepine and GABAA (bicucullin-sensitive) receptor sites was increased and 48 hours after treatment discontinuation the number of GABAB (bicucullin nonsensitive) sites was decreased. The enhanced binding to GABAA and GABAB receptor sites and the decreased binding to benzodiazepine receptors was observed 24 hours after discontinuation of chronic treatment with diazepam (5 mg/kg, twice daily). Forty-eight hours after diazepam chronic treatment was discontinued the number of benzodiazepine receptor sites was increased. The involvement of the increased benzodiazepine receptor sensitivity in the mechanism of therapeutic activity of fenibut is suggested.

[Effect of the GABA receptor blockader bicuculline on the action of fenibut and diazepam]. / Vliianie blokatora GAMK-retseptorov bikukullina na éffekty fenibuta i diazepama.

Fenibut (100 mg/kg) suppressed the motility and emotional reactivity but did not possess any antiaggressive properties, whereas diazepam (2.5 mg/kg) did increase the motility and reduced aggressiveness in rats. Bicuculline (1.25 mg/kg) itself did not cause any behavioral changes, although it was capable of antagonizing the effects of diazepam and to potentiate those of fenibut. Bicuculline attenuated the GABA rise but did not influence the increased content of HVA and DOPAC after fenibut. The importance of the bicuculline-insensitive mechanisms in the action of fenibut and bicuculline-sensitive ones in the action of diazepam is discussed.

[Uniform regulation of central and peripheral benzodiazepine binding sites by GABA receptor agonists in rats]. / Odinakovaia reguliatsiia tsentral'nykh i perifericheskikh mest sviazyvaniia benzodiazepinov agonistami retseptorov GAMK u krys.

Central and peripheral benzodiazepine binding sites were studied in vitro after the administration of GABAA and GABAB agonists. Cerebral cortex and kidney homogenates were used in this study. Muscimol (1.5 mg/kg, intraperitoneally) pretreatment significantly increased the affinity of benzodiazepine binding sites not only in the cerebral cortex but also in the kidneys. Similar changes were obtained with (-) and (+) baclofen (5 mg/kg, intraperitoneally), with the only exception that (-) baclofen in addition to changes in the affinity caused a marked decrease in the number of binding sites in both structures studied. The mechanism of action of GABA agonists on peripheral benzodiazepine binding sites is discussed.

[Fenibut binding with bicuculline-insensitive GABA receptors in the rat brain]. / O sviazyvanii fenibuta s bikukullinnechuvstvitel'nymi retseptorami GAMK v mozge krys.

(+/-) Fenibut beta-phenyl-GABA) was not able to displace 3H-GABA in Na+ independent GABA binding (IC50 greater than 250 microM). Nevertheless, (+/-) fenibut and (+/-) baclofen effectively displaced 3H-GABA in Ca2+ dependent GABA binding in the presence of 50 microM (+) bicuculline. (+/-) Fenibut was less potent in this respect. It is suggested that fenibut may act via bicuculline-insensitive GABA receptors.

[Modulating effect of cerulein on benzodiazepine receptors]. / Moduliruiushchee vliianie tseruleina na benzodiazepinovye retseptory.

Subcutaneous administration of caerulein (100-500 micrograms/kg) significantly reduced the development of picrotoxin (8 mg/kg) seizures in male mice. The same doses of caerulein inhibited 3H-flunitrazepam binding in in vivo experiments. Proglumide, an antagonist of cholecystokinin receptors, in low dose (5 mg/kg) potentiated the effects of caerulein (100 micrograms/kg), whereas the administration of proglumide in high dose (25 mg/kg) reduced the action of caerulein on 3H-flunitrazepam binding and picrotoxin seizures. Caerulein (5-1000 nM) decreased 3H-flunitrazepam binding in in vitro experiments only after supplementation of the binding medium with 120 mM NaCl and 5mM KCl. The results suggest the possible interaction of caerulein with chloride ionophor. It seems probable that the direct interaction of caerulein with chloride ionophor in involved in the inhibitory effect of caerulein on picrotoxin seizures and 3H-flunitrazepam binding.

[Effect of an imidazobenzodiazepine (RO 15-1788) on aggressive behavior in mice]. / Vliianie imidazobenzodiazepina (RO 15-1788) na agressivnoe povedenie myshei.

Imidazobenzodiazepine (Ro 15-1788, 5 mg/kg) similarly to a lose dose of apomorphine (0.1 mg/kg) decreased the intensity of footshock aggression in male rats. Ro 15-1788 significantly potentiated the antiaggressive action of apomorphine. Pirenperone (0.01 mg/kg) potentiated the effect of both drugs, whereas haloperidol (0.01 mg/kg) had an opposite action. After long-term treatment with apomorphine and Ro 15-1788 the tolerance to their antiaggressive action developed. This change was in agreement with increased serotonin metabolism in the forebrain. Unlike the action on aggressive behavior, Ro 15-1788 similarly to haloperidol (0.05 mg/kg) decreased the motor depressant effect of apomorphine (0.01 mg/kg) in mice. This effect correlated with the lowered serotonin metabolism after Ro 15-1788 administration. Unlike apomorphine, Ro 15-1788 reversed catalepsy induced by haloperidol (0.25 mg/kg). Administration of pirenperone (0.03 mg/kg) and destruction of serotoninergic terminals by p-chloroamphetamine (2 X 15 mg/kg) significantly potentiated the sedative action of apomorphine. It appears that different action of Ro 15-1788 on behavioral effects of apomorphine is related to different influence of Ro-1788 on serotoninergic processes in the striatum and limbic structures.