Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.
There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.
Meneses
Alfredo
A
Departamento Pharmacobiology, CINVESTAV-IPN, Tenorios # 235, Granjas Coapa, México City 14330, México. ameneses@msn.com
D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
C472242:DR-4004; D007211:Indoles; D010636:Phenols; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin