Do serotonin1–7 receptors modulate short and long-term memory?

Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT1B receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT1A (WAY100635), 5-HT1D (GR127935), 5-HT2A (MDL100907), 5-HT2C/2B (SB-200646), 5-HT3 (ondansetron) or 5-HT4 (GR125487), 5-HT6 (Ro 04-6790, SB-399885 and SB-35713) or 5-HT7 (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that ‘5-HT tone via 5-HT1B receptors’ might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT1A, 5-HT2A, 5-HT2B/2C, 5-HT4, or 5-HT6 receptors.