Oxotremorine attenuates retrograde amnesia induced by post-training administration of the GABAergic agonists muscimol and baclofen

https://doi.org/10.1016/0163-1047(91)90255-OGet rights and content

These experiments examined the involvement of cholinergic influences in the effects of GABAergic drugs on 24-h retention of an inhibitory avoidance response by mice. A first set of experiments confirmed previous findings indicating that post-training injections (ip) of the GABAergic agonists muscimol (1.0 and 2.0 mg/kg) and baclofen (10.0 and 20.0 mg/kg) impaired retention, as well as previous findings indicating that injections of the cholinergic agonist oxotremorine (5.0 and 10.0 μg/kg) enhanced retention. The findings of a second set of experiments indicated that the memory-impairing effects of muscimol and baclofen were attenuated by concurrent injections of a low, and otherwise ineffective, dose of oxotremorine (2.5 μg/kg). These findings are interpreted as suggesting that GABAergic drugs affect memory storage through influences on cholinergic systems.

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    Some scholars have also noted a similar phenomenon in the AY-9944 models and transgenic GABABR models of atypical absence seizures of Lennox–Gastaut syndrome [32]. Moreover, the administration of GABABR antagonists improves cognitive performance [32–34], whereas GABABR agonists impair learning and memory [35–38]. In the WAG/Rij rats, another model of absence seizure, a decrease in presynaptic GABABR function in the neocortex has been demonstrated to contribute to neocortical hyperexcitability [39].

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Supported in part by USPHS Grant MH12526 from NIMH and NIDA and Office of Naval Research Contract N000014-90-J-1626. We thank Ines Introini-Collison and Nancy Collett for their assistance in the preparation of the manuscript.

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