Effects of 5-HT4 receptor agonists and antagonists in learning.
In the present work, the effects of pre- or post-training (ip) injection of BIMU1 and BIMU8 (5-HT4 agonists) were figured out in the autoshaping learning task. Furthermore, the post-training effects of these agonists after treatment with SDZ 205-557 and GR 125487D (5-HT4 antagonists) or p-Chloroamphetamine (PCA) were also explored. Animals were individually trained in a lever-press response on the autoshaping task and 24 hours later were tested. The results showed that pre-training injection of BIMU1 (5 20 mg/Kg) or BIMU8 (20 mg/Kg) increased the CR; in contrast, the post-training administration of BIMU1 (10-20 mg/Kg) or BIMU8 (5 and 20 mg/Kg) decreased it. Further experiments revealed that the post-training injections of SDZ 205-557 (1.0-10.0 mg/Kg) or GR 125487D (0.39-1.56 mg/Kg) by themselves did not alter the CR. When BIMU1 or BIMU8 was administered to rats pretreated with SDZ 205-557 (10 mg/Kg) or GR 125487D (0.78 mg/Kg), the decrement induced by 5-HT4 the agonists was reversed; in contrast, the administration of PCA failed to modify the CR or the agonist-induced responses. The findings showed that the pre-training stimulation of 5-HT4 receptors enhanced the acquisition of CR, while, post-training activation of 5-HT4 receptors, impaired the consolidation of learning. The latter effect was not altered by PCA pretreatment. The data show that 5-HT4 receptors are involved in the acquisition and consolidation of learning. It seems that postsynaptic 5-HT4 receptors are involved in the latter effect.
Meneses
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Terapeutica Experimental Depto. de Farmacología y Toxicología, CINVESTAV-IPN, Tepepan, México D.F.
Hong
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D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C070187:(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide; C070189:(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide; D010133:p-Chloroamphetamine