Baclofen, a selective GABAB receptor agonist, dose-dependently impairs spatial learning in rats. 1996

R K McNamara, and R W Skelton
Department of Psychiatry, University of Florida, Gainesville, FL 32610, USA.

The present investigation assessed the effects of the selective GABAB receptor agonist baclofen (1, 3, and 6 mg/kg) on spatial learning in the Morris water maze, an aversively motivated spatial learning task. Potential anxiolytic and sedative effects of baclofen were also assessed in an open field. Baclofen dose-dependently reduced locomotion in the open field but had little effect on thigmotaxia (anxiety). In the water maze, baclofen dose-dependently impaired spatial learning and reduced swim speed. During the probe trial given after training, only rats treated with the highest dose of baclofen (6 mg/kg) failed to show a bias for the correct quadrant. Following four additional retraining trials, a second drug-reversal probe trial was given and it was found that rats switched from saline to the highest dose of baclofen (6 mg/kg) showed a bias for the correct quadrant, as did rats switched from the two lowest doses of baclofen (1 and 3 mg/kg) to saline. Rats switched from the highest dose of baclofen (6 mg/kg) to saline failed to show a quadrant bias. Performance on a visible platform task was not impaired by baclofen at any dose. Together these results suggest that baclofen resembles GABAA agonists/positive modulators in that it impairs spatial learning, but not performance of a previously acquired escape response; but differs in that it does not reduce thigmotaxia (anxiety). Potential mechanisms by which baclofen impairs mnemonic processes are discussed.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001418 Baclofen A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. Baclophen,Chlorophenyl GABA,Apo-Baclofen,Atrofen,Ba-34,647,Ba-34647,Baclofen AWD,Baclofène-Irex,Baclospas,CIBA-34,647-BA,Clofen,Gen-Baclofen,Genpharm,Lebic,Lioresal,Liorésal,Nu-Baclo,PCP-GABA,PMS-Baclofen,beta-(Aminomethyl)-4-chlorobenzenepropanoic Acid,beta-(p-Chlorophenyl)-gamma-aminobutyric Acid,AWD, Baclofen,Apo Baclofen,ApoBaclofen,Ba34,647,Ba34647,Baclofène Irex,BaclofèneIrex,CIBA34,647BA,GABA, Chlorophenyl,Gen Baclofen,GenBaclofen,Nu Baclo,NuBaclo,PMS Baclofen,PMSBaclofen
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D058786 GABA-B Receptor Agonists Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS. GABA-B Agonists,GABA-B Receptor Agonist,Agonist, GABA-B Receptor,Agonists, GABA-B,Agonists, GABA-B Receptor,GABA B Agonists,GABA B Receptor Agonist,GABA B Receptor Agonists,Receptor Agonist, GABA-B,Receptor Agonists, GABA-B
D018755 GABA Agonists Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA). gamma-Aminobutyric Acid Agonists,GABA Agonist,GABA Receptor Agonist,GABA Receptor Agonists,gamma-Aminobutyric Acid Agonist,Acid Agonist, gamma-Aminobutyric,Acid Agonists, gamma-Aminobutyric,Agonist, GABA,Agonist, GABA Receptor,Agonist, gamma-Aminobutyric Acid,Agonists, GABA,Agonists, GABA Receptor,Agonists, gamma-Aminobutyric Acid,Receptor Agonist, GABA,Receptor Agonists, GABA,gamma Aminobutyric Acid Agonist,gamma Aminobutyric Acid Agonists
D018782 Maze Learning Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed) Maze Test,Learning, Maze,Maze Learnings,Maze Tests

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