The GABAB receptor and recognition memory: possible modulation of its behavioral effects by the nitrergic system.
Functional activation of the GABA(B) receptor inhibits learning and memory processes, though discrepant findings, in this context, have also been reported. The present study was designed to investigate the role of the GABA(B) receptor on recognition memory in the rat. For this purpose, the effects induced by the GABA(B) agonist baclofen and the GABA(B) antagonist P-(3-aminopropyl)-P-diethoxymethylphosphinic acid (CGP 35348) on memory were assessed by using the object-recognition task. In addition, the possible involvement of the nitrergic system on GABA(B) receptor's effects was also evaluated by using the same behavioral procedure. This is a working-memory paradigm based on the differential exploration of a new and familiar object. In a first dose-response study, baclofen (0.5, 2, and 4 mg/kg, i.p.), dose-dependently impaired animals' performance in this task, suggesting a modulation of acquisition and storage of information. CGP 35348 (100 and 300 mg/kg, i.p.), counteracted these baclofen-induced performance deficits. The nitric oxide donor molsidomine, at the dose of 4 but not 2 mg/kg, i.p, successfully antagonized the deficits on cognition induced by the highest dose of baclofen (4 mg/kg). These results indicate a) that the GABA(B) receptor is involved in recognition memory and b) that an NO component modulates the effects of the GABA(B) receptor on learning and memory.
Pitsikas
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Department of Medical Pharmacology, University of Milan, via Vanvitelli 32, 20129 Milan, Italy. nikpit@yahoo.it
Rigamonti
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Cella
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Muller
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008981:Molsidomine / Q000494:pharmacology; D026602:Nitrergic Neurons / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D014665:Vasodilator Agents; C066430:CGP 35348; D008981:Molsidomine; D001418:Baclofen