The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task

The study examined the effects of modulation of dopamine D2 receptors-mediated neurotransmission in the rat's prefrontal cortex (PFC) on storage and executive components of working memory. Rats were trained on delayed (delay interval, 3 s) and non-delayed choice in a U-maze. The prominence of proactive interference was evaluated by sorting errors in a current trial on the basis of animal reactions in a preceding trial. The erroneous runs to the same arm of the maze as in the previous trial were identified as the repetitions (RE) and the erroneous runs to the other arm in comparison with the previous trial were classified as alternations (AE). The bilateral microinfusion of D2 agonists PPHT (0.004 microg, 0.04 microg, 0.4 microg/1 microl) into medial wall of the PFC produced a dose-dependent increase in the error rate of the delayed-response task and did not influence non-delayed choice. In delay condition PPHT enhanced the perseverative tendencies (the rate of RE was significantly higher than the rate of AE), in non-delayed choice the erroneous performance was mainly represented by AE. In contrast, the infusion of D2-receptor antagonist sulpiride (0.03 microg, 0.3 microg, 3 microg/1 microl) increased the accuracy of delayed choice and changed the mode of intertrial dependence-rats made significantly more AE than RE. The results are discussed in terms of the involvement of D2 receptor dependent transmission of the PFC in different cognitive processes related to the delayed performance in U-maze (within-trial short-term storage of information versus dynamic control of between-trials working memory processing).     

Comparative evaluation of the tolerability of proxofelin and clofelin and their effects on the eye in patients with glaucoma

Tolerance and effects of proxofelin (1% proxodolole and 0.25% clofelin) and clofelin were compared in 39 patients (50 eyes) with primary open-angle glaucoma by open and double-blind methods. Intraocular pressure, ocular hydrodynamics, arterial pressure, and heart rate were examined before and on day 28 of treatment. The hypotensive effect of proxofelin was more expressed than that of clofelin, the drugs decreasing intraocular pressure by 37 and 27% of the initial value, respectively. Proxofelin decreased ophthalmic tone, significantly increasing the coefficient of fluid discharge easiness by 50% and decreasing the production of aqueous humor by 51.9%, while clofelin slightly (14%) increased the coefficient of fluid discharge easiness and decreased intraocular pressure mainly at the expense of suppressing aqueous humor secretion. Hence, the combined drug is preferable in comparison with the monopreparation. Moreover, proxofelin was well tolerated by the patients, which differs it favorably from clofelin.     

The resistance of Plasmodium falciparum strains to preparations of the 4-aminoquinoline series in the Republic of Guinea]

In vivo measurements of P. falciparum sensitivity to chloroquine diphosphate, carried out in the Republic of Guinea, resulted in isolation of strains with degrees I and II resistance from 5 of the 25 examined patients, that may be due to a wide prophylactic administration of the drug to all patients with fevers without completing the course of therapy in all the patients infected. Such courses are obligatory to prevent the dissemination of chloroquine-resistant strains of the parasite and augmentation of the resistance. Further use of chloroquine and its analogs for the prevention and chemoprophylaxis of malaria in the Republic of Guinea appears still desirable, because the majority of P. falciparum strains are still sensitive to these agents. If no favorable changes are detectable in the clinical parameters of malaria patients in 4-5 days of chloroquine treatment or the condition recurs in 1.5-2 months, assessment of P. falciparum sensitivity to chloroquine is advisable, followed by a rational choice of the drug.     

Fast neurotransmission in the rat medial preoptic nucleus

The functional properties of neurotransmission in the medial preoptic nucleus (MPN) were studied in a brain slice preparation from young male rats. The aims were to evaluate the thin slice preparation for studying evoked synaptic responses in MPN neurons, to characterize the fast responses triggered by activation of presynaptic nerve fibers in the MPN, and to identify the involved receptor types. Presynaptic stimulation within the MPN evoked postsynaptic voltage and current responses that were blocked by 200 microM Cd2+ or by 2.0 microM tetrodotoxin and were attributed to action potential-evoked transmitter release. The relation to stimulus strength and comparison with spontaneous synaptic currents suggested that in many cases only one presynaptic nerve fiber was excited by the stimulus. Furthermore, the transmission was probabilistic in nature, with frequent failures. Thus, response probability, most likely reflecting transmitter release probability, could be evaluated in the thin slice preparation. Evoked excitatory postsynaptic currents recorded under voltage-clamp conditions were, due to kinetics, I-V relation, and pharmacological properties, attributed to AMPA/kainate receptors and NMDA receptors, whereas inhibitory currents were attributed to GABAA receptors. No responses that could be attributed to glycine or other types of primary transmitters were detected. Although serotonin (5-HT) did not appear to function as a primary transmitter, glutamate- as well as GABA-mediated transmission was suppressed by 500 microM 5-HT, with a clear reduction in response probability observed. 5-HT also reduced the frequency, but not the amplitude, of spontaneous postsynaptic currents and was therefore ascribed a presynaptic site of action.