Memory time-course: mRNA 5-HT1A and 5-HT7 receptors

In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT1A and 5-HT7 receptors in memory formation, their mRNA expression was determined by RT-PCR in key brain areas for explicit and implicit memory. The time-course (0–120 h) of autoshaped responses was progressive and mRNA 5-HT1A or 5-HT7 receptors expression monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively. At 24–48 h acutely 8-OH-DPAT (0.062 mg/kg) administration enhanced memory and attenuated mRNA 5-HT1A < 5-HT7 receptors expression respect to saline group. WAY100635 (0.3 mg/kg) or SB-269970 (10.0 mg/kg) did not affect the former, partially blocked or reversed the latter, respectively. Furthermore, lower WAY100635 (0.001–0.1 mg/kg) or SB-269970 (1.0–5.0 mg/kg) doses plus 8-OHDPAT not affected memory; however both combinations suppressed or up-regulated mRNA expression 5-HT1A or 5-HT7 receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT7 and 5-HT1A receptors expression. Together these data revealed that, when both 5-HT1A and 5-HT7 receptors were stimulated by 8-OHDPAT under memory consolidation, subtle changes emerged, not evident at behavioral level though detectable at genes expression. Notably, high levels of efficient memory were maintained even when serotonergic tone, via either 5-HT1A or 5-HT7 receptor, was down- or up-regulated. Nevertheless, WAY100635 plus SB-269970 impaired memory consolidation and suppressed their expression. Considering that serotonergic changes are prominent in AD patients with an earlier onset of disease the present approach might be useful in the identification of functional changes associated to memory formation, memory deficits and reversing or even preventing these deficits.