Activation of 5-HT_1A and 5-HT₇ receptors enhanced a positively reinforced long-term memory

Memory is one of the most important capabilities of our mind since it determines our individuality. Memory formation involves different stages: acquisition, consolidation and retrieval. There are many studies about early stages, however little is known about memory retrieval. Retrieval is the use of learned information and represents a big problem in patients with memory deficits where the main issue is that they can learn but cannot remember. Previous findings have demonstrated that 5-hydroxytryptamine (5-HT) is a neurotransmitter involved in memory process. Hence, here we are exploring the role of 5-HT in memory retrieval by using its metabolic precursor l-tryptophan and several ligands at 5-HT_1A and 5-HT₇ receptors. Experimental protocol consisted of evaluating conditioned responses (%CR) after one week of interruption following autoshaping sessions for memory formation; a decrease of %CR was interpreted as memory decay. Systemic administration of: (1) l-tryptophan (50 and 100 mg/kg), (2) 5-HT_1A receptor agonist 8-OH-DPAT (0.031 and 0.062 mg/kg), (3) the selective antagonist 5-HT_1A receptor WAY 100635 (0.3 and 0.6 mg/kg), (4) the 5-HT₇ receptor agonist, LP 211, in a dose-dependent manner (1, 2.5, 5.0 and 10.0 mg/kg) enhanced memory retrieval. Further, the 5-HT₇ receptor antagonist, SB 269970 (10.0 mg/kg), had no effect. Finally, SB 269970 (10.0 mg/kg) significantly blocked memory retrieval enhancement produced by 10.0 mg/kg LP 211, but not that induced by 2.5 mg/kg LP 211.These results, taken together, suggest that activation of 5-HT_1A and 5-HT₇ receptors enhanced memory retrieval and these receptors may be therapeutic targets to improve long-term memory retrieval.