Review 5-HT system and cognition A. Meneses * Departamento de Farmacologı ´a y Toxicologı ´a, CINVESTAV-IPN, AP 22026, Me ´xico D.F. 14000, Mexico Received 22 January 1999; received in revised form 2 June 1999; accepted 23 September 1999 Abstract The study of 5-hydroxytryptamine (5-HT) system has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT 1 to 5-HT 7 ). Growing evidence suggests that 5-HT is important in learning and memory and all its receptors might be implicated in this. Actually, 5-HT pathways, 5-HT reuptake site/transporter complex and 5-HT receptors show regional distribution in brain areas implicated in learning and memory. Likewise, the stimulation or blockade of presynaptic 5-HT 1A , 5-HT 1B , 5-HT 2A/2C and 5- HT 3 receptors, postsynaptic 5-HT 2B/2C and 5-HT 4 receptors and 5-HT uptake/transporter sites modulate these processes. Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders. Further investigation will help to specify the 5-HT system nature involvement in cognitive processes, pharmacotherapies, their mechanisms and action sites and to determine under which conditions they could operate. In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5-HT 1A , 5-HT 1B/1D , 5-HT 2A/2B/2C , 5-HT 4 and 5- HT 7 receptors could constitute a new therapeutic opportunity for learning and memory alterations.  1999 Elsevier Science Ltd. All rights reserved. Keywords: Learning; 5-HT receptors; Memory; Consolidation; Serotonin Contents 1. Introduction ............................................................................ 1111 2. 5-HT receptors occur in brain areas involved in learning and memory ..................................1112 3. 5-HT 1A receptors manipulation on behavioral cognitive tests .........................................1113 3.1. Pre- and post-synaptic 5-HT 1A receptors ................................................... 1115 3.2. 5-HT 1A receptors: agonism, inverse agonism and antagonism .................................... 1115 3.3. 5-HT 1A receptors co-localization with other 5-HT receptors ..................................... 1116 4. 5-HT 1B/1D and 5-HT 2A/2B/2C receptors manipulation on cognitive behavioral tests ..........................1116 5. 5-HT 1B/1D receptors: agonism, inverse agonism and antagonism .......................................1116 6. 5-HT 2A/2B/2C receptors: agonism or inverse agonism and antagonism ...................................1117 7. 5-HT 3 receptor .......................................................................... 1117 8. 5-HT 4 receptors ......................................................................... 1118 9. 5-HT 1E , 5-HT 1F , 5-HT 5A/5B , 5-HT 6 , 5-HT 7A/7B and 5-HT P receptors .....................................1119 10. 5-HT uptake/transporter complex .............................................................1119 11. Concluding remarks ...................................................................... 1120 Acknowledgements ......................................................................... 1120 References ................................................................................ 1120 1. Introduction Most preclinical studies indicate that the investigation on serotonin (5-hydroxytryptamine, 5-HT) is a rapidly expand- ing field, with recent 5-HT receptor discoveries, their possible functions and the new highly specific compound synthesis. Growing evidence indicates that 5-HT system is involved in learning and memory processes [78,79]. For instance, a Medline search as [5-HT and memory] or [5-HT and learning] produced 394 or 1512 articles. Reviews concerning 5-HT drug effect on cognitive processes have Neuroscience and Biobehavioral Reviews 23 (1999) 1111–1125 PERGAMON NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS NBR 416 0149-7634/99/$ - see front matter  1999 Elsevier Science Ltd. All rights reserved. PII: S0149-7634(99)00067-6 www.elsevier.com/locate/neubiorev * Tel.: +52-5675-9075; fax: +52-5675-9168. E-mail address: ameneses@df1.telmex.net.mx (A. Meneses)