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Selective effects of L-glutamate and L-aspartate on retention of an active avoidance response in rats
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42 A SERUM PROTEIN COMPLEX THAT INDUCES CEREBELLAR GRANULE CELL DIFFERENTIATION AND CONFERS FULL RESISTANCE TO THE CYTOTOXICITY CARRIED BY EXCITATORY AMINOACIDS. Cinzia Galli, Patrizia Gulla', M.Teresa Ciotti, M.Liguori, D.Mercanti and Pietro Calissano, Institute of Neurobiology, CNR, Viale Marxl5, 00156 Rome, ITALY. We have identified in rabbit serum a protein complex (NOAF) which, in absence of serum, induces neurite outgrowth and cell adhesion in 8-days-old rat cerebellar cultures.We have compared NOAF-cultured and 10% foetal calf serum cultured cerebellar granules cells in terms of: i) 3H-glutamate-binding, ii) cytotoxic action of excitatory aminoacids (EAA), iii) 45Calcium entry stimulated by EAA and other agonists. The results obtained show that NOAF-cultured granule cells er~hibit: similar extent of 3H-glutamate binding, a full resistance to the cytotoxic action of 1001xM glutamate, kainate and NMDA and markedly reduced 45Calcium entry stimulated by EAA, KCI cr Veratridine-induced depolarization. Other serum-deprived culture conditions which lead to granule cell differentiatio~ do not confer resistance. Shifting cells from 10% serum to NOAF results in a rapid (hours) onset of resistence to EAA-mediated cytotoxic action. These findings demonstrate that the same protein complex which induces granule cell survival and differentiation is also capable of modulating their response to the excitatory aminoacids.
43 NMDA ISOSTERIC AND ALLOSTERIC ANTAGONISTS INTERACT WITH DI RECEPTORS IN MODULATING DOPAMINERGIC FUNCTION. Ottavio Gandolfi, Rossella Dall'Olio and Nicola Montanaro, Institute of Pharmacology, University of Bologna. The kinetic characteristic of DI and D2 specific bindings to striatal synaptic membranes were studied in the presence or in the absence of APV or MK-8OI. APV increased, in a concentration-related manner, Kd values of /-3H~-SCH 23390 specific binding, MK-801 being 20 times weaker in producing the same effect. Bmax values were unchanged by both drugs. In contrast both antagonists failed to modify the kinetic characteristics of /-3 H ~-spiroperidol binding to D2 receptors. Despite this difference APV antagonized both SKF 38393-induced grooming behavior (specific DI -mediated behavior) and LY 171555- elicited hypermotility (specific D2 response). These results, taking into account the primary role of D| receptors in DA-mediated responses, suggest that NMDA antagonists could modulate dopaminergic function by acting postsynaptically. According to this view, NMDA antagonists might modify the conformation of DI recognition site (changing the affinity for DA), indirectly by acting on a process coupled to the function of NMDA receptors.
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SELECTIVE EFFECTS OF L-GLUT~4ATE AND L-ASPARTATE ON RETENTION OF AN ACTIVE AVOIDANCE RESPONSE IN RATS V, G e o r g i e v , D, Y o n k o v , and T, Kambourova Department of E x p e r i m e n t a l Pharmacology, Inst. of Physiology, Bulg. Acad. Sci. Acad. G. Bonchev st., bl. 23, 1113 Sofia, Bulgaria The g l u t a m a t e r g i c t r a n s m i s s i o n is suspected to play an important role in learning and memory. In the following studies the effects of systemically administered l-glutamate, l-aspartate and the antagonist glutamic acid d i e t h y l e s t e r (GDEE) in shuttle box aversive learning retention (active avoidance, AA) of rats was assessed. Retention testing was performed 24 h and 7 days after treatment with the drugs a d m i n i s t e r e d immediately after training procedure. 5 mg/kg of 1-glutamate and of l-aspartate s i g n i f i c a n t l y f a c i l i t a t e d retention at both intervals. GDEE (300 mg/kg) blocked the r e t e n t i o n - i m p r o v i n g effect of both 1-glutamate and l-aspartate. The results suggest that 1-glutamate and l-aspartate can interfere with the retention of AA response.
42 A SERUM PROTEIN COMPLEX THAT INDUCES CEREBELLAR GRANULE CELL DIFFERENTIATION AND CONFERS FULL RESISTANCE TO THE CYTOTOXICITY CARRIED BY EXCITATORY AMINOACIDS. Cinzia Galli, Patrizia Gulla', M.Teresa Ciotti, M.Liguori, D.Mercanti and Pietro Calissano, Institute of Neurobiology, CNR, Viale Marxl5, 00156 Rome, ITALY. We have identified in rabbit serum a protein complex (NOAF) which, in absence of serum, induces neurite outgrowth and cell adhesion in 8-days-old rat cerebellar cultures.We have compared NOAF-cultured and 10% foetal calf serum cultured cerebellar granules cells in terms of: i) 3H-glutamate-binding, ii) cytotoxic action of excitatory aminoacids (EAA), iii) 45Calcium entry stimulated by EAA and other agonists. The results obtained show that NOAF-cultured granule cells er~hibit: similar extent of 3H-glutamate binding, a full resistance to the cytotoxic action of 1001xM glutamate, kainate and NMDA and markedly reduced 45Calcium entry stimulated by EAA, KCI cr Veratridine-induced depolarization. Other serum-deprived culture conditions which lead to granule cell differentiatio~ do not confer resistance. Shifting cells from 10% serum to NOAF results in a rapid (hours) onset of resistence to EAA-mediated cytotoxic action. These findings demonstrate that the same protein complex which induces granule cell survival and differentiation is also capable of modulating their response to the excitatory aminoacids.
43 NMDA ISOSTERIC AND ALLOSTERIC ANTAGONISTS INTERACT WITH DI RECEPTORS IN MODULATING DOPAMINERGIC FUNCTION. Ottavio Gandolfi, Rossella Dall'Olio and Nicola Montanaro, Institute of Pharmacology, University of Bologna. The kinetic characteristic of DI and D2 specific bindings to striatal synaptic membranes were studied in the presence or in the absence of APV or MK-8OI. APV increased, in a concentration-related manner, Kd values of /-3H~-SCH 23390 specific binding, MK-801 being 20 times weaker in producing the same effect. Bmax values were unchanged by both drugs. In contrast both antagonists failed to modify the kinetic characteristics of /-3 H ~-spiroperidol binding to D2 receptors. Despite this difference APV antagonized both SKF 38393-induced grooming behavior (specific DI -mediated behavior) and LY 171555- elicited hypermotility (specific D2 response). These results, taking into account the primary role of D| receptors in DA-mediated responses, suggest that NMDA antagonists could modulate dopaminergic function by acting postsynaptically. According to this view, NMDA antagonists might modify the conformation of DI recognition site (changing the affinity for DA), indirectly by acting on a process coupled to the function of NMDA receptors.
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SELECTIVE EFFECTS OF L-GLUT~4ATE AND L-ASPARTATE ON RETENTION OF AN ACTIVE AVOIDANCE RESPONSE IN RATS V, G e o r g i e v , D, Y o n k o v , and T, Kambourova Department of E x p e r i m e n t a l Pharmacology, Inst. of Physiology, Bulg. Acad. Sci. Acad. G. Bonchev st., bl. 23, 1113 Sofia, Bulgaria The g l u t a m a t e r g i c t r a n s m i s s i o n is suspected to play an important role in learning and memory. In the following studies the effects of systemically administered l-glutamate, l-aspartate and the antagonist glutamic acid d i e t h y l e s t e r (GDEE) in shuttle box aversive learning retention (active avoidance, AA) of rats was assessed. Retention testing was performed 24 h and 7 days after treatment with the drugs a d m i n i s t e r e d immediately after training procedure. 5 mg/kg of 1-glutamate and of l-aspartate s i g n i f i c a n t l y f a c i l i t a t e d retention at both intervals. GDEE (300 mg/kg) blocked the r e t e n t i o n - i m p r o v i n g effect of both 1-glutamate and l-aspartate. The results suggest that 1-glutamate and l-aspartate can interfere with the retention of AA response.