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Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice.
Gen Pharmacol. 1998 Jul; 31(1):81-6.GP

Abstract

1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists on acquisition of a step-down passive avoidance learning in mice was measured in the presence and absence of physostigmine. 2. Intraperitoneal injection of different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg) increased acquisition in mice dose dependently. The maximum response was obtained with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the learned response. To show the effect of the GABAergic system on acquisition, GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not the GABAB receptor agonist baclofen decreased the acquisition of the learned task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased by both muscimol and baclofen. A combination of both agonists caused a higher inhibitory effect on the physostigmine response. 4. Pretreatment of animals with the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and GABAB receptor antagonists reduced the learning improvement induced by physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen increased the impairment of learning induced by muscimol, whereas a combination of either of the antagonists with baclofen did not alter the learning. The GABAA antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of phaclofen increased the inhibition of the physostigmine response induced by muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen decreased but a higher dose of bicuculline increased the baclofen-induced inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB activation inhibit improvement of acquisition induced by physostigmine.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9595284

Citation

Zarrindast, M R., et al. "Effects of GABAergic Drugs On Physostigmine-induced Improvement in Memory Acquisition of Passive Avoidance Learning in Mice." General Pharmacology, vol. 31, no. 1, 1998, pp. 81-6.
Zarrindast MR, Lahiji P, Shafaghi B, et al. Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice. Gen Pharmacol. 1998;31(1):81-6.
Zarrindast, M. R., Lahiji, P., Shafaghi, B., & Sadegh, M. (1998). Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice. General Pharmacology, 31(1), 81-6.
Zarrindast MR, et al. Effects of GABAergic Drugs On Physostigmine-induced Improvement in Memory Acquisition of Passive Avoidance Learning in Mice. Gen Pharmacol. 1998;31(1):81-6. PubMed PMID: 9595284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice. AU - Zarrindast,M R, AU - Lahiji,P, AU - Shafaghi,B, AU - Sadegh,M, PY - 1998/5/22/pubmed PY - 1998/5/22/medline PY - 1998/5/22/entrez SP - 81 EP - 6 JF - General pharmacology JO - Gen Pharmacol VL - 31 IS - 1 N2 - 1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists on acquisition of a step-down passive avoidance learning in mice was measured in the presence and absence of physostigmine. 2. Intraperitoneal injection of different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg) increased acquisition in mice dose dependently. The maximum response was obtained with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the learned response. To show the effect of the GABAergic system on acquisition, GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not the GABAB receptor agonist baclofen decreased the acquisition of the learned task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased by both muscimol and baclofen. A combination of both agonists caused a higher inhibitory effect on the physostigmine response. 4. Pretreatment of animals with the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and GABAB receptor antagonists reduced the learning improvement induced by physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen increased the impairment of learning induced by muscimol, whereas a combination of either of the antagonists with baclofen did not alter the learning. The GABAA antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of phaclofen increased the inhibition of the physostigmine response induced by muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen decreased but a higher dose of bicuculline increased the baclofen-induced inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB activation inhibit improvement of acquisition induced by physostigmine. SN - 0306-3623 UR - https://www.unboundmedicine.com/medline/citation/9595284/Effects_of_GABAergic_drugs_on_physostigmine_induced_improvement_in_memory_acquisition_of_passive_avoidance_learning_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306362397004412 DB - PRIME DP - Unbound Medicine ER -