Behavioural Brain Research 184 (2007) 81–90 Research report Stimulation of 5-HT 1A , 5-HT 1B , 5-HT 2A/2C , 5-HT 3 and 5-HT 4 receptors or 5-HT uptake inhibition: Short- and long-term memory Alfredo Meneses ∗ Depto. de Farmacobiolog´ ıa, Cinvestav, Mexico Received 5 June 2007; accepted 26 June 2007 Available online 6 July 2007 Abstract In order to determine whether short- (STM) and long-term memory (LTM) function in serial or parallel manner, serotonin (5-hydroxtryptamine, 5-HT) receptor agonists were tested in autoshaping task. Results show that control-vehicle animals were modestly but significantly mastering the autoshaping task as illustrated by memory scores between STM and LTM. Thus, post-training administration of 8-OHDPAT (agonist for 5-HT 1A/7 receptors) only at 0.250 and 0.500mg/kg impaired both STM and LTM. CGS12066 (agonist for 5-HT 1B ) produced biphasic affects, at 5.0 mg/kg impaired STM but at 1.0 and 10.0mg/kg, respectively, improved or impaired LTM. DOI (agonist for 5-HT 2A/2C receptors) dose-dependently impaired STM and, at 10.0 mg/kg only impaired LTM. Both, STM and LTM were impaired by either mCPP (mainly agonist for 5-HT 2C receptors) or mesulergine (mainly antagonist for 5-HT 2C receptors) lower dose. The 5-HT 3 agonist mCPBG at 1.0 impaired STM and its higher dose impaired both STM and LTM. RS67333 (partial agonist for 5-HT 4 receptors), at 5.0 and 10.0mg/kg facilitated both STM and LTM. The higher dose of fluoxetine (a 5-HT uptake inhibitor) improved both STM and LTM. Using as head-pokes during CS as an indirect measure of food-intake showed that of 30 memory changes, 21 of these were unrelated to the former. While some STM or LTM impairments can be attributed to decrements in food-intake, but not memory changes (either increase or decreases) produced by 8-OHDPAT, CGS12066, RS67333 or fluoxetine. Except for animals treated with DOI, mCPBG or fluoxetine, other groups treated with 5-HT agonists 6 h following autoshaping training showed similar LTM and unmodified CS–head-pokes scores. © 2007 Elsevier B.V. All rights reserved. Keywords: Autoshaping; 5-HT receptors; Learning rat 1. Introduction Growing evidence from invertebrate [2,3,4,27] and mam- malian species, including human shows [66,67] that serotonin (5-hydroxytryptamine, 5-HT) systems play a role in memory consolidation, short- (STM) and long-term memory (LTM) [7,21,39,44]. In mammalian species, these cognitive processes occur in brain areas such as hippocampus, amygdala, caudate nucleus, hypothalamus and cortex. Significant changes in brain 5-HT systems function and receptors appear as results of mem- ory formation, aging and Alzheimer’s disease (see [44,49], for review; also [11,17,29,32,36,39,47,49,50,57,69]). Notably, using receptor binding profiles, common secondary messenger coupling and functional activity ligands, seven families of 5- hydroxytryptamine receptors and subtypes (5-HT 1A/1B/1D/1E/1F , ∗ Tel.: +52 55 50612869; fax: +52 55 50612863. E-mail address: ameneses@msn.com. 5-HT 2A/2B/2C , 5-HT 3A/3B , 5-HT 4A/4B , 5-HT 5A/5B , 5-HT 6 and 5-HT 7A/7B/7C/7D ) have been identified [18,19,61,62]. Timely questions are the nature of memory [14], including the phar- macological, molecular and theoretical basis of STM and LTM. It is unknown if STM is merely a step towards LTM, or both are separate entities [23,25]. Direct participation of 5-HT has been demonstrated in human and animals by decreasing 5-HT brain levels using acute 5-HT depletion, which impaired memory for- mation (see [12,65,67] for reviews); in contrast, enhancing brain serotonin activity by means of its precursor (i.e., tryptophan) improved memory in animals ([15], see [51], for review). This evidence is consistent with the result that post-training (but not pre-) administration of 5-HT uptake inhibitors improved memory consolidation by increasing 5-HT intersynaptic con- centrations, requiring protein and mRNA synthesis of multiple 5-HT receptors ([40–42]; see also e.g., [50]). This notion is consistent with the fact that 5-HT itself displays a differential affinity for 5-HT receptors [40]. 5-HT systems might exert their effects directly and/or by modulating neurotransmitters such as 0166-4328/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2007.06.026