Memory time-course: mRNA 5-HT1A and 5-HT7 receptors.
In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT(1A) and 5-HT(7) 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-HT(1A) or 5-HT(7) 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-HT(1A)<5-HT(7) 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-HT(1A) or 5-HT(7) receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT(7) and 5-HT(1A) receptors expression. Together these data revealed that, when both 5-HT(1A) and 5-HT(7) 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-HT(1A) or 5-HT(7) 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.
Perez-Garcia
Georgina
G
Departamento de Farmacobiología, CINVESTAV-IPN, México, Mexico. mimigingin@gmail.com
Meneses
Alfredo
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage; D013997:Time Factors
C505862:AS 19 compound; D010636:Phenols; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; C404922:SB 269970; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin