EFFECTS OF THE BENZODIAZEPINE ANTAGONIST FLUMAZENIL ON LEARNING AND MEMORY IN RATS AND ITS POSSIBLE INTERACTION WITH MUSCARINIC CHOLINERGIC RECEPTORS

Abstract

It has been known that different benzodiazepines and central muscarinic cholinergic blockers effect, disturb learning and memory. In this study, benzodiazepine receptor antagonist flumazenil (Ro 15-1788) was given to rats in order to test its effects on l'earning and memory processing and retrieval Scopolamine, a blocker of acethylcholine receptor was given with the intensions of both producing experimental amnesia and investigating possible interactions between cholinergic system and endogenous benzodiazepine receptors. The results of our study showed that benzodiazepine receptor antagonist flumazenil enhances learning and prevents amnesia which has been produced experimentally in rats by scopolamine and facilitates retrieval and the dindings that we achieved were supported by literatüre also.

Keywords

• Amnesia
• benzodiazepine
• flumazenil
• memory
• learning
• scopolamine.

SIÇANLARDA BENZODİAZEPİN ANTAGONİSTİ FLUMAZENİLİN ÖĞRENME VE HAFIZAYA ETKİSİ VE MUSKARİNİK KOLİNERJİK RESEPTÖRLERLE MUHTEMEL ETKİLEŞİMİ

Abstract

Çeşitli benzodiazepinlerin ve santral muskarinik kolinerjik reseptör blokerlerinin öğrenme ve hafızayı etkilediği, bozduğu bilinmektedir. Sunulan çalışmada, sıçanlara benzodiazepin reseptör antagonisti flumazenil (Ro 15-1788) vererek öğrenme ve hafızanın oluşumuna, tekrar çağrılmasına etkisini incelemek, muskarinik asetilkolin reseptör blokeri olan skopolamini ise hem deneysel amnezi oluşturmak hem de kolinerjik sistem ile endojen benzodiazepin reseptörleri arasındaki muhtemel etkileşimleri araştırmak amaçlanmıştır. Araştırmamızın sonuçları, benzodiazepin reseptör antagonisti flumazenil'in öğrenmeyi hızlandırdığını, skopolamin ile sıçanlarda deneysel olarak oluşturulan amneziyi engellediğini ve hatırlamayı kolaylaştırdığını göstermekte ve elde ettiğimiz bulgular literatürce de desteklenmektedir.

Keywords

• Amnezi
• benzodiazepin
• flumazenil
• hafıza
• öğrenme
• skopolamin.

References

1. 1. Currajn HV Schifano F Lader M : Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood. Psychopharmacology (Berlin), 103 (1) : 83-90, 1991.
2. 2. Decker M W Tran T Mc Gaugh JL : A Comparison of The Effects of Scopolamine and Diazepam on Acquisit,ion and Retention of Inhibitory Avoidance in Mice. Psychopharmacology, 100 (4) : 515-521, 1990.
3. 3. File S Pellow S : Intrinsic Actions of Benzodiazepine Receptor Antagonist Ro 15-1788. Psychopharmacology, 88 : 1-11, 1986.
4. 4. lzquierdo I Cünha C Medina JH : Endogenous benzodiazepine modulation of memory processes. Neuroscience Biobhavior Revievv. 14 (4) : 419-424, 1990.
5. 5. Izquierdo I Media JH : GABA A Reseptör Modulation of Memory : The Role of Endogenous Benzodiazepines. Trends in Pharmacological Sciences, 12 (7) : 260-265, 1991.
6. 6. Karavokiros KA Tsipis GB : Flumazenil : A benzodiazepine antagonist. DICP, 24 (10) : 976-981, 1990.
7. 7. Lal H Kumar B Forster MJ : Enhancement of Learning and Memory in Mice by a Benzodiazepine Antagonist. The FASEB Journal, 2 (11) : 2707-2711, 1988.
8. 8. McKay AC McKinney MS Clarke RSJ : Effect of Flumazenil on Midazolam-Induced Amnesia. British Journal of Anaesthesia, 65 ; 190-196, 1990.

9. 9. Preston GC Ward CE Broks P Traub M Stahl SM : Effects of Lorazepam on Memory, Attention and Sedation in Man : Antagonism by Ro 15-1788. Psychopharmacology, 97 (2) : 222-227, 1989.
10. 10. Preston GC Ward C Lines CR Poppleton P Haigh JRM Traub M : Scopolamine and Benzodiazepine Models of Dementia : Cross-reversals by Ro 15-1788 and Physostigmine. Psychopharmacology, 98 (4) : 487-494, 1989.
11. 11. Raffalli MJ Chapouthier S and G : Similar Effects of a Betacarboline and of Flumazenil in negatively and Positively Reinforced Learning Task in Mice. Life Sciences, 48 (7) : 685-692, 1991.
12. 12. Raffalli M İ Chapouthier G Venault P Dodd RH : Methyl /3-Carboline-3-Carboxylate Enhances Performancc in a Multiple-Trial Learning Task in Mice. Pharmacology Biochemist:-y and Behavior, 35 : 281-284, 1990.
13. 13 Urbancic M Gadek MA Marczynski TJ : Chronic Exposure to Flumazenil : Anxiolytic Effect and Increased exploratory Behavior. Pharmacology Biochemistry and Behavior, 35 : 503-509, 1990.
14. 14 Wolfman C Da Cünha C Jerusalinsky D Stein LM Viola H Izquierdo I Medina JH : Habituation and Inhibitory Avoidance Training Alter Brain Regional Levels of Benzodiazepine-like Molecules and are Affected by Intracerebral Flumazenil Microinjection. Brain Research, 548 : 74-80, 1991.